Kingdom of Bahrain Arabian Gulf University College of Medicine and Medical Sciences

1. Kingdom of BahrainArabian Gulf UniversityCollege of Medicine and Medical Sciences Unit IV – Problem 6 – Clinical Disease of Pituitary Gland Prepared by: Ali JassimAlhashli Based on: Kaplan Step 2 CK Internal Medicine

2. Diseases of The Anterior Pituitary • Microadenomas vs. macroadenoma: • Microadenoma: it is > 1 cm in diameter and more common than macroadenomas. • Macroadenoma: it is < 1 cm in diameter and can compress the optic chiasm resulting in visual disturbances such as (bitemporalhemianopia). • Pituitary adenomas by function: • Prolactin-secreting: 50-60%. • Growth hormone-secreting: 15-20%. • ACTH-secreting: 10-15%. • Gonadotroph-secreting: 10-15% • Hyperprolactinemia: • Definition: increased levels of prolactin in the blood. • Etiology: • Natural physiologic conditions: pregnancy, early nursing, stress and nipple stimulation. • Prolactinomas (most common and composing 50-60% pf functioning pituitary adenomas): they are microadenomas in females (because the condition will be detected earlier due to presence of red flags in females; most important being amenorrhea) and macroadenomas in males (compressing optic chiasma and causing visual abnormalities. • Dopamine antagonists (such as metoclopramide and phenothiazines). • Primary hypothyroidism: which results increased TRH release from hypothalamus which in turn stimulates the release of prolacting from adenohypophysis. • Clinical manifestations: • Females: galactorrhea, amenorrhea (↑prolactin inhibiting GnRH thus there is no release of LH and FSH), decreased libido and infertility. • Males: erectile dysfunction, decreased libido, infertility, gynecomastia is rare. • Diagnosis: • Remember always to exclude: pregnancy, lactation, medications and primary hypothyroidism. • ↑prolactin + MRI of brain. • Treatment: • Dopamine agonists: cabergoline or bromocriptine. • Surgery is reserved for: cases not responding to medical therapy or macroadenomas with compressive symptoms. • If even surgery fails: radiation.

3. Diseases of The Anterior Pituitary

4. Acromegaly: • Definition: it is a syndrome of increased Growth Hormone (GH) secretion. In children, it results in gigantism. Acromegaly is gradual (9 years of symptoms before being diagnosed!), chronic debilitating disease associated with bony and soft tissue overgrowth and increased mortality. • Etiology: • Pituitary macroadenoma. • Ectopic tumor: secreting GH or Growth Hormone Releasing Hormone (GHRH). • Clinical presentation: • Headache and visual disturbances (because the cause is a macroadenoma). • Enlargement of hands, feet, nose, mandible and coarse facial features. • Deeper voice. • Enlargement of the heart, lungs, liver, spleen and kidneys. • Osteoarthritis and capal tunnel syndrome. • Menstrual irregularities in females due to co-secretion of prolactin with GH-secreting tumor. • Glucose intolerance (80% of patients) and diabetes (20% of patients). • 1/3 of patients will have hypertension. • There is accelerated atherosclerosis, hypertrophic cardiomyopathy and arrhythmias. Most common cause of death in these patients is due to cardiovascular diseases. • Diagnosis: • Best initial test: ↑IGF-1 level. • Then, confirm with glucose loading test (100 g): normally glucose must completely suppress GH release. If GH level remains high after giving glucose → this confirms the diagnosis of acromegaly. • MRI of the head to localize the macroadenoma. • Treatment: • Start the patient with somatostatin agonists (best medical therapy) such as octreotide to cause regression in the size of the tumor. • Then, do transphenoidalsurgey (which is the PRIMARY TREATMENT OF ACROMEGALY). • Continue the patient with octreotide after surgery because there might be residuals from the tumor which could not be removed. • If medical therapy and surgery fail → radiation (its effect will take nearly up to 3 years to appear during which the patient will continue taking somatostatin analogs). Diseases of The Anterior Pituitary

5. Diseases of The Anterior Pituitary

6. Hypopituitarism: • Definition: it is partial or complete loss of function of the anterior pituitary gland. Notice that GH and gonadotropins (FSH and LH) are lost earlier. • Etiology: • Trauma, radiation, surgery or infections (TB or syphilis). • Large pituitary tumors or hypothalamic tumors. • Pituitary adenomas: most common cause of panhypopituitarism (because they are compressing the remaining of pituitary gland resulting in its necrosis). • Pituitary apoplexy: it is an acute hemorrhagic infarction of pre-existing pituitary adenoma. Clinical presentation: severe headache, nausea/vomiting and depressed mental status. • Sheehan postpartum necrosis (initial sign being the inability to lactate). • Clinical findings: • Deficiency of gonadotropins (FSH and LH): • Females: amenorrhea, infertility, genital atrophy, decreased libido and decreased pubic and axillary hair. • Males: impotence, infertility, testicular atrophy, decreased libido and decreased pubic and axillary hair. • Deficiency of GH is not clinically detectable in adults but in children it will result in failure of growth and short stature. • Deficiency of TSH resulting in hpothyroidism (fatigue/weakness, cold-intolerance, constipation, weight gain and puffy skin). • Deficiency of ACTH results in secondary adrenal insufficiency (decreased response to stress, weight loss and fatigue). Remember that aldosterone secretion is not regulated by ACTH. • Diagnosis: • Gonadotropins deficiency: males (LH, FSH and testosterone); females (LH, FSH and estrogen). • Growth hormone deficiency: measure GH and IGF-1. Then, confirm with insulin-induced hypoglycemia: normal response is increase in GH secretion → if GH remains low this confirms the presence of GH deficiency. • TSH deficiency: ↓T3 and T4 with ↓TSH. • ACTH deficiency: detected by metyrapone test. Metyrapone normally blocks cortisol production which must result in increased ACTH production → if ACTH remains low → this confirms your diagnosis of ACTH deficiency. • Management: first and most important hormone to be replaced is cortisol. Then, replace other deficient hormones. • Empty Sella Syndrome (ESS): • Definition: herniation of suprasellarsubarachenoid space through an incomplete diaphragm sella. • Etiology: idiopathic or secondary to trauma/radiation. • Clinical presentation: most patients are obese, multiparaous females with headaches. • Diagnosis: no pituitary gland can be seen with CT/MRI of the head! • Treatment: reassurance. Diseases of The Anterior Pituitary

7. Diseases of The Anterior Pituitary

8. Diabetes Insipidus (DI): • Definition: • Central DI: partial or complete deficiency in the secretion of ADH. • Nephrogenic DI: there is normal secretion of ADH but renal receptors are resistant. • Etiology: • Central DI: severe head injury, infections (meningitis), surgery of hypothalamus/pituitary, radiation or hypothalamus/pituitary tumors. • Nephrogenic DI: hypercalcemia, hypokalemia, amyloidosis, pyelonephritis, Sjogren syndrome, myeloma, sickle cell disease or drugs (lithium, colchicine and demeclocycline). • Clinical presentation: • Patient will present with polyuria (inability to retain free water) and poyldypsia. • There will be hypernatremia (↑serum osmolarity). • Dilute urine (↓urine osmolarity with urine specific gravity >1.010). • Diagnosis: • Water deprivation test: water restriction normally will result in decreased urine volume with concentrated urine. In patients with DI, even with fluid restriction urine volume will remain high and it will be dilute. With central DI → ADH level is low while with nephrogenic DI → ADH level is high. • Management: • Central DI: desmopressin (DDAVP: intranasally). • Nephrogenic DI: hydrochlorothiazides. Diseases of The Posterior Pituitary

9. Diseases of The Posterior Pituitary

10. Syndrome of Inappropriate Secretion of ADH (SIADH): • Definition: there is increased secretion of ADH. • Etiology: • CNS disease: stroke, trauma or encepahlitis. • Pulmonary disease: pneumonia, TB or asthma. • Malignancies: lung cancer and cancers of pancreas and duodenum. • Drugs: SSRIs, tricyclic antidepressants, haloperidole, vincristine and carbamazepine. • Clinical presentation/diagnosis: • ↓urine volume and urine will be concentrated (urine osmolarity< 300 mOsm). • Hyponatremia and ↓serum osmolarity. If hyponatremia has acute onset, there is a high risk for seizures and coma. • ↑ADH level. • Management: • Restriction of fluids to 800-1000 ml/day (to increase serum sodium concentration). • V2-receptor antagonists. • If hyponatremia is severe and causing patient to seize or enter a state of coma → 3% hypertonic saline (but notice that correction of sodium must no exceed 12 mEq/24 hours). Diseases of The Posterior Pituitary