pediagenosis: Endocrine
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Showing posts with label Endocrine. Show all posts
Showing posts with label Endocrine. Show all posts

Saturday, May 8, 2021

Energy Homoeostasis Central Control

Energy Homoeostasis Central Control


Energy Homoeostasis Central Control
Clinical scenario
PG, a 15-year-old boy, presented to the paediatric endocrine clinic with delayed puberty and complaining of thirst and polyuria. Investigations revealed hypopituitarism and diabetes insipidus caused by a craniopharyngioma, a cystic tumour of the hypothalamus. He was treated with surgery and radiotherapy. Postoperatively he had deficiencies of all the anterior pituitary hormones requiring hormone replacement and persistent diabetes insipidus treated with DDAVP (see Chapter 35). In the year following treatment he gained 22 kg in weight. He found it extremely difficult to control his food intake and his mother noticed he would continue to eat any food that was in front of him. Attempts to follow a calorierestricted diet failed.

Energy Homoeostasis: II Central Control

Energy homeostasis is controlled by the integration of autonomic input and peripheral signals by the brain. Hypothalamic regions involved in this process have been identified in experimental systems, predominantly involving two neuronal populations, the orexigenic neuropeptide Y/Agouti-related peptide neurones and the anorexic pro-opiomelanocortin/ cocaine and amphetamine-related transcript (CART) system. These are interconnected and affected by a number of hormones including insulin, glucocorticoids and leptin. It is likely that the hypothalamic obesity syndrome seen in patients with diseases of the hypothalamus and suprasellar regions relates to disruption of these homeostatic mechanisms.
Energy Homoeostasis Summary

Energy Homoeostasis Summary


Energy Homoeostasis Summary
Clinical background
In recent years, adipose tissue has become recognized as a highly metabolically active organ. In 1994, the hormone leptin was identified, a peptide almost exclusively secreted by adipose cells and with receptors both in the hypothalamus and peripheral tissues. Leptin has a number of actions both in relation to signalling satiety and altering energy metabolism. The identification of a rare family with leptin deficiency, extreme obesity and insulin resistance was followed by treatment of two children with recombinant leptin and successful loss of weight. However, in the majority of non-leptin-deficient obese individuals, circulating leptin levels are high and correlated with body fat mass, suggesting that leptin resistance may play a role in human obesity. Further work is needed to establish the exact role of this hormone in energy homeostasis.

Energy Homoeostasis: I Summary

Endocrine hormones and energy metabolism
The neuroendocrine system plays a critical role in energy metabolism and homeostasis and is implicated in the control of feeding behaviour. Energy metabolism centres on the maintenance of an adequate supply of glucose for metabolism and on the balance between energy storage and utilization (Fig. 44a). The rapid spread of obesity, with attendant diabetes and heart disease, in western affluent societies has promoted research that has identified previously unknown endocrine hormones that regulate, and indeed dictate, feeding behaviour in other species (see below and Chapter 45).
Obesity Causes of Obesity

Obesity Causes of Obesity


Obesity Causes of Obesity
Clinical background
Obesity is a global problem in public health and rates of obesity are increasing throughout the world (Fig. 46a). The World Health Organization has defined obesity as ‘abnormal or excessive fat accumulation in adipose tissue to the extent that health is impaired’. Obesity is associated with an increased risk of Type 2 diabetes, hypertension, hyperlipidaemia, cardiovascular disease, sleep apnoea syndrome and respiratory failure, subfertility, arthritis and gallbladder disease. Targets are set using the measurement of Body Mass Index (BMI; weight [kg] / height2 [m2]) (Table 46.1).
Obesity: I Causes of Obesity

The relationship between BMI and comorbidities (Fig. 46b) may vary between ethnic groups and certain studies use different cut-off points for that reason. Special charts have been developed to examine obesity rates in children. As central adiposity is associated with a higher risk of metabolic disorders, the waist hip ratio or straightforward waist measurement has been widely used to identify high-risk groups.
Obesity Cardiovascular and Respiratory Complications

Obesity Cardiovascular and Respiratory Complications


Obesity Cardiovascular and Respiratory Complications
Clinical background
Obesity is associated with a number of complications and comorbidities. Cardiovascular disease is the major cause of death in obese patients and there is a direct link between the degree of obesity and the degree of hypertension. Other risk factors for coronary heart disease, such as smoking and hyper- lipidaemia, should be addressed. There is also a higher risk of thromboembolism and stroke in the obese population. Other complications include osteoarthritis, back pain, ligament and tendon injury, gallstones and an increased risk of certain cancers, in particular those of the colon, rectum, breast, endometrium and prostate (Fig. 47a). Sleep apnoea syndrome is more common in the obese, particularly men.

Respiratory complications of obesity

Cardiovascular complications of obesity
Obesity not only relates to but also predicts coronary atherosclerosis in both men and women, even with minimal increases in BMI (Fig. 47b). Disordered lipid metabolism occurs partly through decreased levels of the enzyme lipoprotein lipase, an insulin-sensitive enzyme that breaks down fat. This results in elevated serum triglycerides and reduced HDL  cholesterol. Hyperglycaemia results in the glycation of more LDL, which increases the affinity of LDL for the modified LDL receptors on macrophages. This in turn promotes endothelial cell cyto- toxicity, foam cell production and smooth muscle proliferation. Plasminogen activator inhibitor (PAI-1) is raised (Fig. 47b), and this prothrombic state is a further risk factor for coronary artery disease. Elevated circulating levels of C-reactive protein, a systemic marker of inflammation, also occur as increased visceral fat appears to enhance the inflammatory pathway response that involves phospholipase A2, intracellular adhesion molecule and C-reactive protein.
Obesity Insulin Resistance and Endocrine Complications

Obesity Insulin Resistance and Endocrine Complications


Obesity Insulin Resistance and Endocrine Complications
Clinical background
Metabolic syndrome
Obesity is associated with a number of metabolic consequences characterized by insulin resistance and hyperlipidaemia. These in turn contribute to the increased risk of cardiovascular disease and diabetes (Fig. 48a and Table 48.1). Metabolic syndrome is the term given to a range of metabolic disturbances occurring in the same patient, all of which should be addressed and modified. Patients with metabolic syndrome have insulin resistance, which precedes the onset of hypertension and Type 2 DM and is thought to represent the primary pathological disturbance. Metabolic syndrome thus describes insulin resistance, hyperinsulinaemia, hypertension, hypertriglyceridaemia, low HDL- cholesterol and obesity. Patients with metabolic syndrome are at a high risk of macrovascular disease and treatment should be aimed at improving insulin sensitivity by diet and exercise and aggressive treatment of hyperlipidaemia.
 Obesity: III Insulin Resistance and Endocrine Complications, Type 2 diabetes
Polycystic ovary syndrome and insulin resistance Obesity is found in around 50% of women with polycystic ovary syndrome (PCOS; see Chapter 26). Furthermore, lean women with PCOS demonstrate lesser degrees of hyperinsulinaemia and insulin resistance, which play a role in the pathogenesis of PCOS independently of obesity as insulin stimulates ovarian androgen production. The metabolic consequences of obesity and hyperinsulinaemia are seen in women with PCOS who have a high risk of developing impaired glucose tolerance and Type 2 diabetes. Clinical evidence of hyperinsulinaemia may be seen as acanthosis nigricans, a brown velvety pigmentation usually seen at the base of the neck and in the axillae in obese women with PCOS.
Calcium Parathyroid Hormone

Calcium Parathyroid Hormone


Calcium Parathyroid Hormone
Clinical scenario
A 55-year-old woman, Mrs CB, had a routine blood test at her general practitioners and was found to have a serum calcium level of 2.88 mmol/L. She was referred to the local endocrine clinic. She was completely asymptomatic, having none of the classical symptoms associated with hypercalcaemia such as bone pain, abdominal pains, renal colic, thirst, polyuria or tiredness. Further investigations confirmed a high serum calcium in association with a low serum phosphate, normal Vitamin D concentrations, a raised 24-hour urine calcium excretion and an elevated serum parathyroid hormone concentration. Sestamibi radioisotope scanning revealed a single abnormality in the upper right parathyroid gland and subsequent surgery confirmed the presence of a single parathyroid adenoma.
 Parathyroid Hormone, parathyroid glands, Physiological actions of PTH, Gastrointestinal tract, Pathophysiology of PTH, Hyperparathyroidism, Hypoparathyroidism
Role of calcium
Calcium is essential for: bone growth, blood clotting, maintenance of the transmembrane potential, cell replication, stimulus contraction and stimulus secretion coupling, and the second messenger process.

Tuesday, April 27, 2021

Calcium Calcitonin

Calcium Calcitonin


Calcium Calcitonin
Clinical background
Medullary thyroid cancer (MTC) is a rare malignancy arising from the parafollicular thyroid C cells that secrete calcitonin. It usually presents as a lump in the thyroid gland or as lymph node metastases in the neck. Diagnosis is made by a biopsy and the treatment is surgical, possibly with adjunctive chemother- apy. MTC may be sporadic or familial and in both types may be associated with phaeochromocytoma or other features of the Multiple Endocrine Neoplasia Type 2 (MEN 2) syndrome (Table 50.1). It is important to distinguish the truly sporadic cases from the first presentation of familial disease as screening can allow early detection and treatment in family members.
Calcitonin, Biosynthesis and secretion, Physiological actions of calcitonin

Calcitonin
Calcitonin is a hypocalcaemic polypeptide hormone. In mammals, it is synthesized and secreted in parafollicular (C) cells in the thyroid gland. C cells have been found in much lower density in the parathyroid glands and in the thymus. In fish and birds, calcitonin is synthesized within a specific organ, the ultimobranchial body. The ultimobranchial bodies do develop in mammals during fetal life, but eventually disappear. It is thought that the C cells evolved before the parathyroids, to help sea-dwelling animals to cope with the relatively high concentrations of calcium in sea water.
Calcium Vitamin D

Calcium Vitamin D


Calcium Vitamin D
Clinical scenario
Mrs BK, a 55-year-old lady of Bangladeshi origin, presented to her GP complaining of various non-specific symptoms including generalized aches and pains and muscle weakness when walking, particularly going upstairs. Investigations showed her to have a serum calcium level of 2.02 mmol/L in association with a raised alkaline phosphatase of 358 U/L and an elevated PTH concentration. Serum vitamin D concentrations were measured and found to be below the seasonal normal range. Her symptoms resolved with calcium and vitamin D supplementation.
Vitamin D deficiency is common, particularly in patients of Asian background and the elderly living alone on poor diets. In northern European populations there is a marked seasonal variation in normal serum concentrations related to varying day-light lengths. Low vitamin D levels cause hypocalcaemia, compensated for by the development of secondary hyperparathyroidism which maintains the serum calcium at low normal or mildly suppressed levels. Untreated, vitamin D deficiency can lead to the development of rickets in children or osteomalacia in adults (Fig. 51a), both associated with characteristic bone abnormalities. Recently an increase in vitamin D deficiency has been noted in children from more affluent European backgrounds with limited sun exposure due to overzealous sun protection.

Calcium: III Vitamin D, Synthesis of vitamin D, Physiological actions of vitamin D Bone

Vitamin D
Vitamins are not generally considered to be hormones, but organic dietary factors essential for healthy life. The term ‘vitamin’ is perhaps a misnomer therefore for the substances called vitamin D. The term ‘vitamin D’ refers to two steroid-like chemicals, namely ergocalciferol and cholecalciferol. Osteomalacia is the softening of bones in adults who suffer from a deficiency of vitamin D in the diet, or of sunlight, or both.
Bone Remodelling

Bone Remodelling


Bone Remodelling
Introduction
The nature of bone. Bone is an essential rigid support for the body, a means of effecting locomotion and a reservoir of ions such as calcium, phosphate, magnesium and sodium. Bone is two-thirds mineral and the rest is mainly type 1 collagen and water. Bone mineral is present mainly as crystalline hydroxyapatite and the rest as amorphous calcium phosphate, which occurs in higher amounts in actively forming, young bone.
Bone needs to be not only rigid and strong but also light enough to allow muscle contractions. These properties are con- ferred by the structure of bone, which in the case of cortical tubular bones consists mainly of densely packed layers of mineralized collagen, and, in the case of the axial skeleton, of spongier trabecular or cancellous bone. Defective cortical bone results in long bone fracture, while defective trabecular bone results in vertebral fractures.

Bone Remodelling, Cellular structure of bone

Cellular structure of bone
Bone matrix is laid down in concentric layers called lamellae. The unit of structure in compact bone is the osteon. In each osteon, lamellae  are  arranged  around  the  central  Haversian canal; the canal houses blood vessels and nerves. The osteocytes are located in the lacunae, which are connected by branching tubules called canaliculi. The canaliculi radiate out from the lacunae to form an extensive network, connecting bone cells to each other and to the blood supply.

Sunday, April 25, 2021

Metabolic Bone Disease Paget ’s Disease

Metabolic Bone Disease Paget ’s Disease


Metabolic Bone Disease Paget ’s Disease
Clinical background
Paget’s disease (osteitis deformans) is a chronic bone disorder resulting in bone pain and deformity. It affects up to 10% of the elderly, more commonly men, although it may be asymptomatic and discovered on a routine blood test or X-ray. Most commonly patients present with bone pain or deformity – these are characteristic of the disorder and include bowing of the long bones, skull enlargement with frontal bossing and, less commonly, pathological fractures (Fig. 53a, b and c).
Metabolic Bone Disease: I Paget ’s Disease
Paget’s disease is characterized by abnormal bone remodelling. Often the disease is picked up by the finding of a high alkaline phosphatase on biochemical screening. Calcium and PTH concentrations are normal but measurements of markers of bone turnover, such as serum bone-specific alkaline phosphatase (BAP) and osteocalcin indicating bone formation and urinary deoxypyridinoline and N-terminal telopeptide indicating bone resorption, may be helpful.
Metabolic Bone Disease Primary Osteoporosis

Metabolic Bone Disease Primary Osteoporosis


Metabolic Bone Disease Primary Osteoporosis
Clinical background
Osteoporosis is a common disease of the elderly, affecting over 2 million women in the UK, and associated with significant morbidity and mortality. It is characterized by ‘fragility fractures’, defined as a fracture occurring after a fall from standing height or less and it is estimated that 33% of women and 20% of men over the age of 80 will sustain a hip fracture due to osteoporosis. Other common sites for osteoporotic fractures include the spine and distal radius (Colles’ fracture) and it is estimated that the cost to the UK National Health Service and social services of treatment for osteoporotic fractures of the hip alone is in the order of £2.3 billion per annum. Primary osteoporosis in women is due to a combination of age and estrogen deficiency; the cause in men is less clear but probably includes age-related falls in both estrogen and androgen concentrations.
Osteoporosis occurs in the context of lifetime changes in bone density. Peak bone density in both males and females is achieved in the late 20’s and age-related bone loss begins at the start of the fifth decade. Peak bone mass is genetically determined and a major predictor of osteoporosis risk in later life. Other factors include sex hormone status, nutrition, calcium and vitamin D status and levels of physical activity. Both men and women exhibit age-related bone loss from the fifth decade, but the process in women is accelerated during the menopause, reflecting the role of estrogen as a major factor in the maintenance of bone mineral density. Osteoporosis is diagnosed by assessing bone mineral density by means of dual-energy X-ray absorptiometry (DEXA) scanning. The patient’s score is measured according to standard deviation scores below normal peak bone mass.
A number of risk factors for osteoporosis have been identified and include age, sex, family history, Caucasian or Asian ethnicity, history of thyroid disease, cigarette smoking and excessive alcohol intake. The major risk factor for fractures in the elderly with osteoporosis is falling. Assessment of the patient should always include risk factors for falling such as visual impairment, cardiovascular disease with syncope, neuromuscular weakness and environmental hazards such as steps or poorly fitting carpets.
Therapeutic intervention may be offered as primary prevention to postmenopausal women, with significant risk factors depending upon their bone density and as secondary prevention following a fracture (see Chapter 55).

Estrogen and osteoporosis

Aetiology
Osteoporosis is loss of bone mass and is the most common metabolic bone disease. Gender, race, heredity, lifestyle and nutrition, particularly the degree of calcium intake during the period of peak bone growth, determine the incidence of osteoporosis (Fig. 54b). The main phases of bone mass change are:
(i) attainment of peak bone mass during postpubertal life and completion of bone mass consolidation between the ages of 20 and 30; (ii) commencement of bone loss between the ages of 30 and 40, which occurs equally in trabecular and cortical bone approximately 25% of bone is lost; and (iii) postmenopausal loss of bone, mainly trabecular (e.g. vertebral), secondary to estrogen loss (Fig. 54a).
Metabolic Bone Disease Secondary Osteoporosis

Metabolic Bone Disease Secondary Osteoporosis


Metabolic Bone Disease Secondary Osteoporosis
Introduction
Osteoporosis may occur as a secondary problem in patients with a range of endocrine and other disorders (Fig. 55a; Table 55.1). A high proportion of patients treated chronically with glucocorticoids develop osteoporosis. It may develop in patients immobilized for long periods, when bone resorption develops with consequent hypercalciuria and hypercalcaemia, especially in younger patients in whom bone turnover is normally rapid. Osteoporosis has been observed in astronauts, presumably due to the loss of gravitational effects, although the aetiology of this phenomenon is unknown. Hereditary disorders of collagen expression and metabolism may result in osteoporosis. These include Ehlers–Danlos syndrome, homocysteinuria and osteogenesis imperfecta.
The vast majority of patients with osteoporosis have the primary condition but causes of secondary osteoporosis should always be sought when undertaking clinical assessment.
Glucocorticoids and osteoporosis Glucocorticoids, used to treat inflammatory disorders, cause osteoporosis, affecting predominantly the trabecular bone of the axial skeleton such that vertebral fractures are more common than those of the hip. Glucocorticoids cause osteoporosis through a wide variety of actions (Fig. 55b).
Direct actions. Glucocorticoids directly inhibit the replication of osteoblast lineages and the biosynthesis of new osteoblast cells and they induce apoptosis of osteoblasts, partially through their interactions with growth factors such as the insulin-like growth factors. In addition, glucocorticoids may directly decrease synthesis of osteocalcin, a component of bone matrix, and stimulate the synthesis of collagenase-3, which breaks down collagen types I and II, essential building blocks of bone. Furthermore, glucocorticoids stimulate osteoclast activity directly, and possibly indirectly, via secondary hyperparathyroidism.
Indirect actions. Glucocorticoids inhibit calcium absorption from the GIT and increase renal excretion, which may contrib- ute to the development of secondary hyperparathyroidism. Glucocorticoids are associated with decreased plasma levels of estrogens and testosterone by suppressing adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland, thus resulting in suppression of adrenal androgen production. Luteinizing hormone production is decreased with consequent lowering of both estradiol and testosterone production in women and men respectively. Glucocorticoids also inhibit growth hormone production. Patients with Cushing’s syndrome, which is associated with excessive adrenal activity, may also be at risk of osteoporosis and fractures.
Glucocorticoid therapy is a major cause of rapid bone loss and primary preventive therapy with bisphosphonates should be prescribed for every patient about to start a course of steroid therapy for more than 3 months.

Metabolic Bone Disease: III Secondary Osteoporosis

Other endocrine disorders
Hyperthyroidism can cause osteoporosis by the direct action of thyroid hormone on bone resorption, since thyroid hormone is normally associated with high bone turnover. Fractures are uncommon in hyperthyroidism due to prompt diagnosis and treatment. Postmenopausal women with osteoporosis and a history of hyperthyroidism are, however, at increased risk of hip fractures. Type 1 diabetes mellitus is associated with mild osteopenia of cortical bone, although there does not seem to be a high incidence of fractures in these patients. Patients with Type 2diabetes mellitus, on the other hand, usually have normal bone mass.

Thursday, April 15, 2021

Introduction To Endocrinology

Introduction To Endocrinology


Introduction To Endocrinology
The endocrine system consists of glands, which secrete hormones that circulate and act at distant sites in the body. The key endocrine glands are the pituitary, thyroid, parathyroids, adrenals, pancreas and gonads. Endocrine disease can lead to hypo- or hypersecretion of hormones. Endocrine diseases include tumours, which are commonly benign, autoimmune diseases, enzyme defects and hormone receptor abnormalities.

Endocrinology, Mechanisms of hormone action, Patterns of hormone secretion, Measurement of hormones, Dynamic endocrine tests

Synthesis, release and transport
The chemical structure of hormones includes steroids, polypeptides, glycoproteins and amines (Figure 1.1). Hormones are secreted by the hypothalamus at low concentration, acting locally on the anterior pituitary, which in turn secretes trophic hormones to the relevant target gland. Hormones are secreted directly into the circulation either in their final form or as a larger precursor molecule, such as proopiomelanocortin (POMC), which is cleaved to adrenocorticotrophic hormone (ACTH), melanocyte stimulating hormone (MSH) and other smaller peptides. Many hormones are transported in the circulation by binding proteins, but only the free hormone acts on the receptor. Examples of binding proteins are sex hormone binding globulin (SHBG), which binds testosterone, and cortisol binding globulin (CBG), which binds cortisol.
The Hypothalamic Pituitary Axis and Its Assessment

The Hypothalamic Pituitary Axis and Its Assessment


The Hypothalamic Pituitary Axis and its Assessment
The pituitary gland is the ‘conductor of the endocrine orchestra’, controlling all peripheral glands via trophic hormones. It is approximately the size of a pea and sits in the pituitary fossa at the base of the brain (Figure 2.1). The anterior pituitary is derived embryologically from Rathke’s pouch, derived from primitive gut tissue. The posterior pituitary is derived from a down-growth of primitive brain tissue. The optic chiasm lies superior to the pituitary gland. Lateral is the cavernous sinus, which contains cranial nerves III, IV and Va and the internal carotid artery (Figure 2.1).

The Hypothalamic Pituitary Axis 2 And Its Assessment, Growth hormone, ACTH, Gonadotrophins (FSH and LH), TSH, Prolactin

Physiology
Hypothalamic releasing and inhibiting factors are transported along the hypophyseal portal tract to the anterior pituitary. There are five pituitary axes: GH, ACTH, gonadotrophins (FSH and LH), TSH and prolactin (Table 2.1).
Acromegaly

Acromegaly


Acromegaly
Acromegaly, meaning ‘large extremities’ in Greek, is almost exclusively caused by a GH-secreting pituitary tumour. Patients have often had acromegaly for many years before the diagnosis is considered. The increased detection of incidental pituitary tumours can lead to early diagnosis if appropriate tests are performed. Untreated acromegaly can lead to disfiguring features and premature death, predominantly from cardiovascular disease.

Acromegaly

Clinical features
Acromegaly is associated with a classic constellation of clinical features (Figure 3.1). Increased size of hands and feet occur commonly, and rings may need to be cut off as they become too tight. Facial features become coarser over time, with frontal bossing of the forehead, protrusion of the chin (prognathism) and widely spaced teeth (Figure 3.2). The diagnosis is often made after the first consultation with a new healthcare professional. Soft tissue swelling leads to enlargement of the tongue and soft palate, snoring and sleep apnoea, and puffiness of the hands with carpal tunnel syndrome. Other specific features of GH hypersecretion include sweating, headaches, hypertension and diabetes mellitus, which may resolve after treatment.
Cushing’s Syndrome

Cushing’s Syndrome


Cushing’s Syndrome
Cushing’s syndrome occurs as a result of increased endogenous or exogenous steroids. The diagnosis is considered when the classic clinical features are recognised. There are several causes of Cushing’s syndrome, but Cushing’s disease specifically refers to an ACTH-secreting pituitary tumour, leading to bilateral adrenal hyperplasia and excess cortisol secretion. Systematic biochemical evaluation is essential to accurately confirm the presence of Cushing’s syndrome and determine the source of excess steroid. Cushing’s syndrome can be a challenging condition both in terms of diagnosis and treatment.

Cushing’s Syndrome

Clinical features
Cushing’s syndrome is characterised by the development of central obesity, a dorso-cervical fat pad and increased roundness of the face. Patients often have a flushed appearance (plethoric) and complain of thin skin, easy bruising and proximal myopathy (Figure 4.1). Patients may present with hypertension, premature osteoporosis and diabetes mellitus. Left untreated, Cushing’s syndrome is associated with significant morbidity and has a 5-year mortality approaching 50%.

Wednesday, April 14, 2021

Hypopituitarism and Non-Functioning Pituitary Adenomas

Hypopituitarism and Non-Functioning Pituitary Adenomas


Hypopituitarism and Non-Functioning Pituitary Adenomas
Non-functioning pituitary adenomas
Non-functioning pituitary adenomas (NFPAs) are bioc cally inert tumours. They usually present with the physical effects of a pituitary mass lesion (e.g. visual field loss, headache and hypopituitarism) or, increasingly, when discovered incidentally on routine brain MRI (‘pituitary incidentalomas’). Surgical decompression is indicated if there is a visual field defect or if the lesion is close to the optic chiasm.
The usual route for removal is trans-sphenoidally, although trans-cranial surgery is occasionally needed. NFPAs can cause hypopituitarism by compressing the normal gland, which requires endocrine replacement. Histologically, NFPAs can have positive immunostaining for inactive LH and FSH, but they do not secret bioactive hormones. Patients with significant postoperative residual tumour may require radiotherapy.

Hypopituitarism And Non-Functioning 5 Pituitary Adenomas

Hypopituitarism
Causes
Hypopituitarism has several causes, either congenital (from pituitary transcription factor defects) or acquired. Acquired hypopituitarism is most commonly caused by the presence of a pituitary tumour. Other acquired causes include inflammatory and infiltratitive disorders, traumatic brain injury and radiotherapy (Figure 5.1). In patients with hypopituitarism and a large empty pituitary fossa on MRI, it is important to enquire about a previous history of severe headache, as this may reflect missed pituitary apoplexy (Chapter 36).

Saturday, April 3, 2021

Endocrine Control Of Reproduction

Endocrine Control Of Reproduction


Endocrine Control Of Reproduction
Reproductive function in males and females is controlled by common hormonal systems based on the hypothalamic control of the pituitary gonadotrophins, individually known as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These glycoproteins are released from the gonadotrophs of the anterior pituitary gland under the influence of gonadotrophin-releasing hormone (GnRH; Chapter
44) (Fig. 50a,b). Failure of GnRH release is one cause of infertility. It is released in pulses at intervals of 1–3 h in both males and females, a pattern that is accurately reflected in plasma levels of LH. The pulsatile pattern of GnRH secretion is essential for normal reproductive activity, as continuous exposure of gonadotrophs to the hormone leads to a rapid desensitization of the gonadotrophs and a reduction in the release of gonadotrophins. The releasing hormone acts through receptors coupled to Gq (Chapter 3) to stimulate the release and manufacture of the gonadotrophins.

Endocrine Control Of Reproduction

Actions of gonadotrophins
The gonadotrophins produce their effects via interactions with guanosine triphosphate-binding protein (G-protein)-coupled receptors that activate the intracellular production of cyclic adenosine monophosphate (cAMP) (Chapter 3). In the male, LH acts on the Leydig cells of the testes to stimulate the production of the steroid testosterone, which acts in concert with FSH on Sertoli cells of the seminiferous tubules to support spermatogenesis (Fig. 50a). Sperm are generated in a two-stage meiosis from spermatocytes via spermatids. Spermatogenesis proceeds most efficiently at a temperature of 34 °C, which is why the testes are located outside the body cavity. A normal adult male produces some 2 × 108 sperm per day, a process that carries on from puberty until the end of life. Sertoli cells also produce inhibin, a peptide feedback signal that specifically inhibits the release of FSH from the anterior pituitary.
The Adrenal Glands And Stress

The Adrenal Glands And Stress


The Adrenal Glands And Stress
The adrenal glands are located just above each kidney (hence the name; Fig. 49a) and consist of two endocrine tissues of distinct developmental origins. The inner core (the adrenal medulla) releases the catecholamine hormones adrenaline (epinephrine) and noradrenaline (norepinephrine). It develops from neuronal tissue and is functionally part of the sympathetic nervous system (Chapter 7). The outer layers of the gland (the adrenal cortex) originate from mesodermal tissue and secrete steroid hormones, primarily under the control of the anterior pituitary gland (Chapter 44). Removal of the adrenal glands in animals results in death within a few days, which is thought to result from the loss of the ability to cope with stress.

The Adrenal Glands And Stress

The adrenal medulla
The chromaffin cells of the adrenal medulla manufacture and secrete noradrenaline (20%) and adrenaline (80%). These catecholamine hormones are derived from tyrosine by a series of steps catalysed by specific enzymes (Fig. 49b). The production of the rate-limiting enzyme, phenylethanolamine-N-methyl transferase, is stimulated by cortisol, providing a direct link between the functioning of the medulla and cortex. The secretion of catecholamines is stimulated by sympathetic preganglionic neurones located in the spinal cord (Chapter 7), so that the adrenal medulla functions in concert with the sympathetic nervous system, of which noradrenaline is the main neurotransmitter. Catecholamine release contributes to normal physiological functions, but is enhanced by stress (see below). Adrenaline and noradrenaline act through guanosine triphosphate-binding protein (G-protein)-coupled adrenoceptors. These are classified as α1, α2 and β1–β3. The hormones have the same effects in tissues as the stimulation of sympathetic nerves, with important stress-related responses being vasoconstriction (α1), increased cardiac output (β1) and increased glycolysis and lipolysis (β2, β3). These actions support increased physical activity. Noradrenaline has equal potency at all adrenoceptors, but adrenaline, at normal plasma concentrations, will only activate β-receptors (NB: higher levels do stimulate α-receptors). Phaeochromocytoma is a tumour of the adrenal medulla that leads to the excess production of catecholamines, with high blood pressure as the most immediately threatening symptom. It is treated by α-adrenoceptor antagonists and/or surgery.
Thyroid Hormones And Metabolic Rate

Thyroid Hormones And Metabolic Rate


Thyroid Hormones And Metabolic Rate
The thyroid gland is attached to the anterior surface of the trachea just below the larynx. It releases two iodine-containing hormones, thyroxine (also known as T4) and tri-iodothyronine (T3; Fig. 45a), the main effect of which is to increase heat production (thermogenesis) throughout the body and thereby induce an increase in metabolic rate. The hormones also have a crucial role in growth and development.
Thyroid Hormones And Metabolic Rate

Synthesis and release
The thyroid gland is formed from clusters of cells (follicles) that surround a gel-like matrix or colloid, the primary constituent of which is the glycoprotein thyroglobulin. The follicle cells actively accumulate iodide (I−) ions by means of an Na+–I− symporter (Chapter 4) driven by the inward sodium gradient (Fig. 45b). The formation of T3 and T4 occurs in two steps: (i) the amino acid tyrosine is iodinated to form mono- (T1) or di-iodotyrosine (T2) (Fig. 45a); (ii) T2 is then coupled to T1 or T2 by thyroperoxidase to form the thyroid hormones. This process occurs with the tyrosine residues attached to thyroglobulin, so that, at any one time, this protein is festooned with molecules of T1, T2, T3 and T4 (Fig. 45b). The thyroid hormones and their intermediates are highly lipophilic and would escape from the gland were they not incorporated into thyroglobulin, which thus acts as a nucleus for the manufacture of the hormones and as a storage site. The hormones are released under the control of thyroid-stimulating hormone (TSH) from the anterior pituitary, which is obligatory for normal thyroid function (Chapter 44; Fig. 45c). Under the action of TSH, thyroid follicle cells pinch off small quantities of colloid by pinocytosis. Lysozymal protease enzymes then act on the thyroglobulin to liberate the iodinated compounds into the cell and thence into the bloodstream (Fig. 45b). Free T1  and T2 are deiodinated by enzymatic action before they can leave the cell. The average plasma concentration of T3 is roughly one-sixth of that of T4, and much of that derives from deiodinated T4. Most of the thyroid hormones in the blood are bound to thyroxine-binding protein and are thus unavailable to their receptors, which are located inside target cells, attached directly to deoxyribonucleic acid (DNA). The small amounts of free T3 and T4 in plasma readily cross the cell membranes to bind to thyroid hormone receptors (the most important of which is TRa1). Thyroid receptors are linked to a DNA sequence known as the thyroid-response element (TRE) which initiates the transcription of thyroid-responsive genes. T3 is some 10 times more potent than T4 in activating TRα1 and consequently mediates most thyroid hormone actions, notwithstanding its lower levels in plasma. Thyroid receptors are present in almost all tissues, with particularly high levels in the liver and low levels in the spleen and testes.

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