Saturday, April 3, 2021
Thursday, April 1, 2021
Thursday, February 4, 2021
SECRETION AND ACTION OF VASOPRESSIN
Vasopressin, also known as antidiuretic hormone (ADH), is the key hormone involved in the regulation of water homeostasis and osmolality of body ﬂuids. The secretion and action of vasopressin are regulated by osmotic and pressure/volume factors. Osmoreceptors continuously monitor plasma osmolality. The osmoreceptors are outside the blood–brain barrier, are located in the organum vasculosum of the lamina terminalis (adjacent to the anterior hypothalamus near the anterior wall of the third ventricle), and are perfused by fenestrated capillaries. The normal extracellular ﬂuid osmolality determined to a major degree by serum sodium concentration varies from 282 to 287 mOsm/ kg in healthy individuals. The keys to maintaining this narrow normal range are (1) the very sensitive osmore-ceptor-regulated response of vasopressin secretion to changes in plasma osmolality, (2) the prompt response of urine osmolality to changes in plasma vasopressin, and (3) the short plasma half-life of vasopressin (~15 minutes). Thus, small increases in plasma osmolality result in a prompt increase in urine concentration, and small decreases in osmolality result in prompt water diuresis.
LANGERHANS CELL HISTIOCYTOSIS IN CHILDREN
Langerhans cell histiocytosis (LCH) previously known as histiocytosis-X, eosinophilic granuloma, Hand-Schüller-Christian disease, or Letterer-Siwe disease is a disorder of the Langerhans cell, a bone marrow–derived dendritic cell that has a key role in antigen processing. Normal Langerhans cells located in the epidermis, lymph nodes, thymic epithelium, and bronchial mucosa process antigens and then migrate to lymphoid tissues, where they function as effector cells stimulating T-cell responses. Although the cause of the defect in LCH is unknown, it is a result of immunologic dysfunction. In LCH, the Langerhans cell loses its ability to present antigens.
CENTRAL DIABETES INSIPIDUS
Diabetes insipidus (DI) literally means a large volume of urine (diabetes) that is tasteless (insipid). Central DI is characterized by a decreased release of antidiuretic hormone (ADH; vasopressin), resulting in polydipsia and polyuria. ADH deﬁciency may be a result of disorders or masses that affect the hypothalamic osmoreceptors, the supraoptic or paraventricular nuclei, or the superior portion of the supraopticohypophyseal tract. Approximately 90% of the vasopressinergic neurons must be destroyed to cause symptomatic DI. Because the posterior pituitary gland stores but does not produce ADH, damage by intrasellar pituitary tumors usually does not cause DI. The most common causes of central DI are trauma (e.g., neurosurgery, closed-head trauma), primary or metastatic tumors, and inﬁltrative disorders. Central DI can be exacerbated by or ﬁrst become apparent during pregnancy, during which ADH catabolism is increased by placental hyperproduction of the enzyme cysteine aminopeptidase (vasopressinase).
SECRETION AND ACTION OF OXYTOCIN
The physiologic roles of oxytocin are smooth muscle activation promoting milk letdown with breastfeeding and uterine myometrial contraction at parturition. The milk-producing compartments of the breast are composed of multiple alveolar clusters of milk-producing (glandular) cells surrounded by specialized myoepithelial cells. Prolactin stimulates milk production in endocrinologically prepared breasts. The alveoli are connected to ductules that lead to large ducts that lead to the nipple. The glandular cells have receptors for oxytocin and cause myoepithelial contraction when activated. In addition, oxytocin acts on ductal myoepithelial cells to enhance milk ﬂow to the nipple. Activation of nipple tactile and mechanoreceptors by suckling sends an afferent signal to the spinal cord and from the spinal cord to the oxytocinergic neurons in the supraoptic and paraventricular nuclei. Oxytocin is then released from the posterior pituitary in a pulsatile fashion that effects a pumping action on the alveoli, promoting emptying of milk from the alveoli. In the absence of oxytocin, only approximately 30% of stored milk is released during nursing. There is a latent period of approximately 30 seconds between the onset of suckling and commencement of milk ﬂow. Psychogenic stimuli can also trigger milk letdown in lactating mothers. Changes in estrogen and progesterone at the time of parturition help modulate the lactation response both by affecting oxytocin synthesis and secretion and by impacting oxytocin receptors.
CLINICALLY NONFUNCTIONING PITUITARY TUMOR
Clinically nonfunctioning pituitary tumors are identiﬁed either incidentally (e.g., on head magnetic resonance imaging [MRI] to evaluate unrelated symptoms) or because of sellar mass-related symptoms (e.g., visual ﬁeld defect). On the basis of autopsy studies, pituitary microadenomas (≤10 mm in largest dimension) are relatively common, present in approximately 11% of all pituitary glands examined. However, pituitary macroadenomas (>10 mm in largest dimension) are uncommon. Immunohistochemical studies on resected pituitary adenomas can determine the adenohypophyseal cell of origin. The most frequent type of pituitary macroadenoma is the gonadotroph cell adenoma; most do not hypersecrete gonadotropins; thus, affected patients do not present with a hormone excess syndrome. The second most common clinically nonfunctioning pituitary macroadenoma is the null cell adenoma that is not basophilic or acidophilic (chromophobe adenoma); this is a benign neoplasm of adenohypophyseal cells that stains negatively for any anterior pituitary hormone on immunohistochemistry. Rarely, lactotroph, somatotroph, and corticotroph pituitary adenomas may be clinically silent.
Nelson syndrome is progressive pituitary corticotroph tumor enlargement after bilateral adrenalectomy is performed for the treatment of pituitary-dependent Cushing syndrome. Although the treatment of choice for a corticotroph adenoma is selective adenectomy at the time of transsphenoidal surgery (see Plate 1-22), bilateral laparoscopic adrenalectomy is indicated when pituitary surgery is not successful. When bilateral adrenalectomy cures hypercortisolism, there is less negative feedback on the corticotroph tumor cells with physiologic glucocorticoid replacement, and the adenoma may grow. Nelson syndrome occurs in a minority of patients who follow the treatment sequence of failed transsphenoidal surgery and bilateral adrenalectomy. Most corticotroph microadenomas do not enlarge over time in this setting. However, when pituitary-dependent Cushing syndrome is caused by a corticotroph macroadenoma (10 mm in largest diameter), the risk of tumor enlargement after bilateral adrenalectomy is high.
Wednesday, October 28, 2020
CORTICOTROPIN-SECRETING PITUITARY TUMOR
Corticotropin (adrenocorticotropic hormone [ACTH])-secreting pituitary adenomas stimulate excess adrenal secretion of cortisol, resulting in the signs and symptoms characteristic of Cushing syndrome (see Plate 3-9). ACTH-secreting pituitary tumors are typically benign microadenomas (10 mm in largest diameter); occasionally, they are macroadenomas, and very rarely they are carcinomas. Treatment of choice for an ACTH-secreting pituitary adenoma is transsphenoidal selective adenectomy. Surgical success is deﬁned as cure of Cushing syndrome and intact anterior and posterior pituitary function.
PROLACTIN-SECRETING PITUITARY TUMOR
Prolactin-secreting pituitary tumors (prolactinomas) are the most common hormone-secreting pituitary tumor. They are monoclonal lactotroph cell adenomas that appear to result from sporadic mutations. Although most prolactinomas are sporadic, they are the most frequent pituitary tumor in persons with multiple endocrine neoplasia type 1 (see Plate 8-1). In addition, more than 99% of prolactinomas are benign. Approximately 10% of prolactin-secreting pituitary tumors cosecrete growth hormone because of a somatotroph or mammosomatotroph component.
Chronic growth hormone (GH) excess from a GH-producing pituitary tumor results in the clinical syndrome of acromegaly. Acromegaly was the ﬁrst pituitary syndrome to be recognized, described by Pierre Marie in 1886. If untreated, this syndrome is associated with increased morbidity and mortality. Although the annual incidence is estimated to be only three per 1 million persons in the general population, a GH-secreting pituitary adenoma is the second most common hormone-secreting pituitary tumor. The effects of the chronic GH excess include acral and soft tissue over- growth, progressive dental malocclusion (underbite), degenerative arthritis related to chondral and synovial tissue overgrowth within joints, a low-pitched sonorous voice, headaches, malodorous hyperhidrosis, oily skin, perineural hypertrophy leading to nerve entrapment (e.g., carpal tunnel syndrome), proximal muscle weakness, carbohydrate intolerance (the initial presentation may be diabetes mellitus), hypertension, colonic neoplasia, obstructive sleep apnea, and cardiac dysfunction. The mass effects of GH-producing pituitary macroadenomas (10 mm) are similar to those of other pituitary macroadenomas and include visual ﬁeld defects, oculomotor pareses, headaches, and pituitary insufﬁciency.
Pituitary gigantism occurs when a growth hormone (GH)–secreting pituitary tumor develops before fusion of the epiphyseal growth plates in a child or adolescent. In contrast, when GH-secreting pituitary tumors develop in an adult (after complete epiphyseal fusion), there is no linear growth, but there are acral changes, and the condition is termed acromegaly (see Plate 1-20). Pituitary gigantism is rare. When it starts in infancy, it may lead to exceptional height. The tallest well- documented person with pituitary gigantism measured 8 ft, 11 in (272 cm). When untreated, pituitary giants are typically taller than 7 ft. The GH-secreting pituitary tumors in individuals with pituitary gigantism are usually sporadic, but they may arise as part of a syndrome such as multiple endocrine neoplasia type 1 (see Plate 8-1), McCune-Albright syndrome (see Plate 4-11), and the Carney complex (see Plate 3-12).
Although pituitary apoplexy, acute hemorrhage of the pituitary gland, is an uncommon event, it is an endocrine emergency, and prompt diagnosis and treatment are critical. The typical presentation is acute onset of severe headache (frequently described as “the worst headache of my life”); vision loss (the hemorrhagic expansion takes the path of least resistance and extends superiorly and compresses the optic chiasm); facial pain; nausea and vomiting; or ocular nerve palsies (e.g., ptosis, diplopia) caused by impingement of the third, fourth, and sixth cranial nerves in the cavernous sinuses. In addition, patients may have signs of meningeal irritation and an altered level of consciousness. Increased intracranial pressure may result in increasing drowsiness and stupor and may mandate surgical intervention and decompression. Hypothalamic involvement may lead to disorders of sympathetic autoregulation, resulting in dysrhythmia and disordered breathing. Erythrocytes and an increased protein concentration are found in the cerebrospinal ﬂuid of many patients with pituitary apoplexy. This may be a potential source of confusion in differentiating pituitary apoplexy from meningitis or subarachnoid hemorrhage.
POSTPARTUM PITUITARY INFARCTION (SHEEHAN SYNDROME)
The pituitary gland enlarges during pregnancy (primarily because of lactotroph hyperplasia) and because of its portal venous blood supply is uniquely vulnerable to changes in arterial blood pressure. In 1937, Sheehan suggested that in the setting of severe postpartum uterine hemorrhage, spasm of the infundibular arteries, which are drained by the hypophysial portal vessels, could result in pituitary infarction. If the lack of blood ﬂow continued for several hours, most of the tissues of the anterior pituitary gland infarcted; when blood ﬁnally started to ﬂow, stasis and thrombosis occurred in the stalk and the adenohypophysis. The necrotic areas of the adenohypophysis underwent organization and formed a ﬁbrous scar. Sheehan speculated that variations in the extent and duration of the spasm account for variations in the extent of the necrosis. Today it is recognized that the basic mechanism is infarction secondary to a lack of blood ﬂow to the adenohypophysis. However, it is actually not clear if the infarction is a result of vasospasm, thrombosis, or vascular compression.
SEVERE ANTERIOR PITUITARY DEFICIENCY OR PANHYPOPITUITARISM
Severe symptoms of anterior pituitary insufﬁciency appear only when destruction of the adenohypophysis is nearly complete. With progressive destruction (75%), mild hypogonadism becomes more severe, and general symptoms attributable to thyroid and adrenal cortical hypofunction, such as asthenia, fatigue, loss of appetite, and cold intolerance, appear and progress. Complete anterior pituitary failure may occur after surgery for a pituitary macroadenoma.
SELECTIVE AND PARTIAL HYPOPITUITARISM
Selective and partial hypopituitarism refers to the loss of at least one but not all pituitary hormones. The term panhypopituitarism is reserved for the syndrome resulting from the loss of all the hormonal functions of the pituitary, including those of the neurohypophysis (see Plates 1-16 and 1-27). The clinical presentation depends on the rapidity of hormone loss (e.g., sudden with pituitary apoplexy [see Plate 1-18] vs. slow with a slowly growing pituitary tumor) and the number of pituitary hormones affected.
PITUITARY ANTERIOR LOBE DEFICIENCY IN ADULTS
Anterior pituitary deﬁciency is decreased secretion of pituitary hormones caused by a disorder of the pituitary or hypothalamus. Compression of a normal pituitary gland by a pituitary adenoma is the most common cause. Other causes of anterior pituitary failure include pituitary cyst, pituitary surgery, pituitary radiation, inﬁltrative lesion (e.g., lymphocytic hypophysitis, hemochromatosis), infarction (e.g., Sheehan syndrome), apoplexy, genetic disorder (e.g., pit-1 mutation, POU1F1 mutation), primary empty sella syndrome, and metastatic disease to the sella. Hypothalamic diseases that may cause varying degrees of hypopituitarism include mass lesions (e.g., craniopharyngioma, germinoma, metastatic disease), radiation (e.g., for brain or nasopharyngeal malignancies), inﬁltrative lesions (e.g., sarcoidosis, Langerhans cell histiocytosis), trauma with skull base fracture, and infection (e.g., viral encephalitis, tuberculous meningitis).
PITUITARY ANTERIOR LOBE DEFICIENCY IN CHILDHOOD AND ADOLESCENCE IN BOYS
The most common deﬁcient hormones in children and adolescents with anterior pituitary failure are the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Gonadotropin deﬁciency may occur in isolation or in concert with other anterior pituitary hormone deﬁciencies. In the absence of gonadotropins in boys, puberty is delayed, and secondary sex characteristics do not develop (see Plate 4-7). The penis and prostate gland remain small, and the scrotum fails to develop rugae; the larynx fails to enlarge, and the voice maintains the high pitch of childhood. Some pubic hair appears, but it is usually sparse and ﬁne. Axillary hair either does not appear or is sparse. Beard growth is absent.
Sunday, October 18, 2020
NONTUMOROUS LESIONS OF THE PITUITARY GLAND AND PITUITARY STALK
The nontumorous lesions of the pituitary gland that can affect function include lymphocytic hypophysitis, granulomatous disorders (e.g., sarcoidosis, tuberculosis, Langerhans cell histiocytosis, Wegener granulomatosis), head trauma with skull base fracture, iron overload states (e.g., hemochromatosis, hemosiderosis), intrasellar carotid artery aneurysm, primary empty sella, pituitary cyst infection (e.g., encephalitis, pituitary abscess), mutations in genes encoding pituitary transcription factors, and developmental midline anomalies.
EFFECTS OF PITUITARY TUMORS ON THE VISUAL APPARATUS
The optic chiasm lies above the diaphragma sellae. The most common sign that a pituitary tumor has extended beyond the conﬁnes of the sella turcica is a visual defect caused by the growth pressing on the optic chiasm. The most frequent disturbance is a bitemporal hemianopsia, which is produced by the tumor pressing on the crossing central ﬁbers of the chiasm and sparing the uncrossed lateral ﬁbers. The earliest changes are usually enlargement of the blind spot; loss of color vision, especially for red; and a wedge-shaped area of defective vision in the upper-temporal quadrants, which gradually enlarges to occupy the whole quadrant and subsequently extends to include the lower temporal quadrant as well.