The hypothalamus and the pituitary gland

Hypopituitarism is an underactive pituitary gland that results in deficiency of one or more pituitary hormones. Hypopituitarism can be caused by several factors, including certain inflammatory disorders, a tumor of the pituitary gland, or an insufficient blood supply to the pituitary gland. Symptoms depend on what hormone is deficient and may include short height, infertility, intolerance to cold, fatigue, and an inability to produce breast milk. The diagnosis is based on measuring the blood levels of hormones produced by the pituitary gland and on imaging tests done on the pituitary gland. Treatment focuses on replacing deficient hormones with synthetic ones but sometimes includes surgical removal or irradiation of any pituitary tumors.

Growth hormone excess: • in children (before epiphyseal fusion) leads to gigantism • in adults (after epiphyseal fusion) leads to acromegaly

Etiology GH secreting pituitary adenoma, carcinoid pancreatic islet tumors secreting ectopic GHRH

Pathophysiology • normally GH is a catabolic hormone that acts to increase blood glucose levels • in growth hormone excess states secretion remains pulsatile but there is loss of hypoglycemic stimulation, glucose suppression, and the nocturnal surge • proliferation of bone, cartilage, soft tissues, organomegaly • insulin resistance and IGT

Clinical Features Enlargement of hands and feet, coarsening of facial features, thickening of calvarium, prognathism, thickening of skin, increased sebum production, sweating, acne, sebaceous cysts, fibromata mollusca, acanthosis nigricans, arthralgia, carpal tunnel syndrome, degenerative osteoarthritis, thyromegaly, renal calculi, hypertension, cardiomyopathy, obstructive sleep apnea, colonic polyps and DM

Investigations Screening by IGF- 1 Confirm the diagnosis by measuring GH levels during an OGTT, In normal subjects, plasma GH suppresses to below 0.5 μg/L . In acromegaly, GH does not suppress and in about 50% of patients there is a paradoxical rise Imaging for localization & determining the cause The rest of pituitary function should be investigated Question: How do you diagnose acromegaly in diabetic patient?

Management Trans-sphenoidal surgery is usually the first line of treatment (More often, surgery serves to debulk the tumor and further second-line therapy is required, according to post-operative imaging and glucose tolerance test results.) External radiotherapy is usually employed as second line treatment if acromegaly persists after surgery, to stop tumor growth and lower GH levels Question: what are the draw back of uses of radiotherapy? In patients with persisting acromegaly after surgery, medical therapy is usually employed to lower GH levels to < 1.5 μg/L (approximately < 5 mU/L) and to normalize IGF-1 concentrations Question: write briefly about the drugs that used in treatment of acromegaly.

Hyperprolactinaemia Hyperprolactinaemia is a common abnormality which usually presents with hypogonadism and/or galactorrhoea (lactation in the absence of breastfeeding). In women ( in addition to hypogonadism and/or galactorrhoea) hyperprolactinaemia causes secondary amenorrhea and anovulation with infertility Q1: explain the rare occurrence of galactorrhoea in male patient. Q2: what is the difference between Macroprolactinoma & macroorloactin?

etiology • pregnancy and breastfeeding • prolactinoma: most common pituitary adenoma • pituitary masses with pituitary stalk compression causing reduced dopamine inhibition of release • primary hypothyroidism (increased TRH) • decreased clearance due to chronic renal failure or severe liver • medications with anti-dopaminergic properties are a common cause of high prolactin levels: antipsychotics (common), antidepressants, anti hyper tensives, anti-migraine agents (triptans/ ergotamines), bowel motility agents (metoclopramide/domperidone), H2-blockers (ranitidine)

Approach to Nipple Discharge • Differentiate between galactorrhoea (fat droplets present) versus breast discharge (usually unilateral, may be bloody or serous) • If galactorrhoea, determine if physiologic (e.g. pregnancy, lactation, stress) versus pathologic • If abnormal breast discharge, must rule out a breast malignancy

Investigations Pregnancy should first be excluded before further investigations are performed in women of child-bearing potential Serum prolactin gonadal function , and T 4 and TSH measured to exclude primary hypothyroidism causing TRH-induced prolactin excess MRI or CT scan of the hypothalamus and pituitary Patients with a macroadenoma also need tests for hypopituitarism

Management Correct the cause if possible Dopamine agonist therapy Question: How do you explain the failure of resumption of gonadal function despite effective lowering of prolactin?

Prolactinoma Microadenoma Macroadenoma Question: how do you explain the fact that the prolactinomas can secrete excess growth hormone and cause acromegaly?

Management Medical ( 1st line) (dopamine agonist) Surgery Radiation (Davidson's principal & practice of medicine, 21st edition, page 790) Surgery a. failure of medicine to shrink the tumor size b. intolerance of dopamine agonists Radiation