Pituitary Hormones Conditions PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Conditions Due to Excess/Deficiency of Pituitary Hormones Department of Medicine LEARNING OUTCOMES Define the conditions related to pituitary hormone excess/deficiency Explain the pathophysiology of pituitary hormo...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Conditions Due to Excess/Deficiency of Pituitary Hormones Department of Medicine LEARNING OUTCOMES Define the conditions related to pituitary hormone excess/deficiency Explain the pathophysiology of pituitary hormone excess/deficiency List the cardinal symptoms of pituitary hormone excess/deficiency List the cardinal signs of pituitary hormone excess/deficiency Explain how symptoms and signs are caused in pituitary hormone excess/deficiency Develop a differential diagnosis for pituitary hormone excess/deficiency CASE 24-year-old woman presents with amenorrhea Menarche was at age 13 Menses became regular at age 15 and remained regular until age 22, when she began to skip periods more and more frequently until age 23, when they stopped completely Two months ago, she began to notice an occasional milky discharge from her nipples. Review of systems: Headaches, no visual or other neurologic complaints. + fatigue, depression, and cold intolerance. Can’t seem to lose weight she gained with last pregnancy. Medications: None On physical examination, skin and hair are normal, as is the pelvic examination. Her breasts are mature, and milk can be expressed bilaterally. CASE Initial evaluation How do you interpret the Pregnancy test negative lab values? TSH Normal What is the next step? Prolactin 6000 mu/l What is the diagnosis? (reference 90 to 500)  PITUITARY HORMONES Distinct hormones secreted by the anterior (adenohypophysis) and posterior (neurohypophysis) lobes of the pituitary gland. Most pituitary hormones secreted by the anterior pituitary gland. Many physiological processes (stress, growth, reproduction, metabolism, lactation, etc.) controlled by the secretion of these hormones. Damage can occur acutely (suddenly) or chronically (slowly, over time), can be considered on a scale of mild to severe, and can affect the secretion of one, several, or all pituitary hormones. Clinical presentation depends on these factors. DISEASES OF THE PITUITARY Tumours : Pituitary Neuroendocrine Tumours – Adenomas that arise from cells of the anterior pituitary. – Can be clinically silent or secretory e.g. Prolactinoma, Corticotroph adenomas, Somatotroph adenomas, TSHoma, or mixed – Rarely may be part of another syndrome – e.g. in multiple endocrine neoplasia (MEN) type 1 syndrome (pituitary adenoma, pancreatic endocrine tumour, and parathyroid tumours), AIP, carney complex, etc Non-pituitary lesions that arise from cell rests (craniopharyngiomas, Rathke’s cleft cysts) in or near the sella turcica INFILTRATIVE DISEASES – sarcoid, hemochromatosis (pituitary) INFLAMMATORY LESIONS: HYPOPHYSISTIS INFECTIONS TRAUMA, HAEMORRAGE , METASTASES, ETC HORMONAL CONSEQUENCES Hypersecretion – Only pituitary adenomas can hypersecrete hormones, or fragments thereof, normally made by pituitary cells Hyposecretion – Any disease of the pituitary or hypothalamus can cause of deficiency of any hormone made by the anterior pituitary PITUITARY HORMONE EXCESS Hyperpituitarism is defined as an excess of one or more hormone normally secreted by the pituitary gland. Mainly but not exclusively relates to a single hormone The most clinically relevant excesses are related to: Anterior: Prolactin Growth Hormone (GH) ACTH TSH-rare FSH / LH-rare  PITUITARY HORMONE EXCESS - SOMATOTROPH ADENOMA –ACROMEGALY Excess of Growth Hormone (GH) causes either gigantism (if the epiphyseal plates are still open during childhood, where longitudinal growth is possible- characterized by tall stature and long extremities) or acromegaly (in adults) GROWTH HORMONE EXCESS/ACROMEGALY Examination Findings: related to GH excess/IGF1 Frontal bossing- exaggerated brow Coarsened facial features Prognanthism and separation of teeth Enlarged feet, hands, tongue Thickened skin face and hands Hyperhidrosis Skin tags Nerve entrapment: carpal tunnel Complications of Acromegaly: Hypertension Also look for signs/symptoms relating to Diabetes Mellitus pituitary mass: Cardiomyopathy Headaches Colon Cancers Blurred vision Bitemporal hemianopia Diplopia Can have signs/symptoms of other pituitary hormone deficiency GROWTH HORMONE EXCESS (ACROMEGALY & GIGANTISM)  SOMATOTROPH ADENOMA - DIAGNOSIS Clinical Suspicion Increased Acts on production IGF-1 GH LIVER Chemical Confirmation & release of – Elevated serum insulin like growth factor-1 (IGF-1) – Lack of suppression of growth hormone to an oral glucose load  SOMATOTROPH ADENOMA GH RESPONSE TO GLUCOSE (NORMAL SUPPRESSION < 0.3 NG/ML) GROWTH HORMONE (ng/mL) 30 Acromegaly 20 10 Acromegaly 0 Normal -30 0 30 60 120 180 TIME (min) 75 grams of Oral Glucose MRI APPEARANCE SOMATOTROPH ADENOMA - CONSEQUENCES Diabetes mellitus Arthritis (osteoarthritis) Cancer, especially of the colon, preceded by polyps Cardiovascular disease-hypertension, cardiomyopathy, strokes Neuropathy, including carpal tunnel syndrome Obstructive sleep apnea, respiratory disease Increased Mortality  PITUITARY HORMONE EXCESS -PROLACTINOMAS/ LACTOTROPH ADENOMA - Lactotroph cells secrete prolactin, which results in hyperprolactinemia Most common type of pituitary adenoma Clinical Syndrome Premenopausal Women – Amenorrhea or oligomenorrhea – Galactorrhea Postmenopausal Women – Pressure symptoms Men – Decreased libido – Decreased fertility – Erectile dysfunction – Galactorrhea (uncommon) – Pressure symptoms PROLACTIN Under tonic inhibition by dopamine released from hypothalamus Elevated prolactin is common in patients with hypothalamic- pituitary lesions (Stalk effect) Low prolactin in the context of pituitary disease indicate severe hypopituitarism CAUSES OF HYPERPROLACTINEMIA Physiologic – Pregnancy – Lactation – Exercise – Physical and psychological stress Pathologic – Lactotroph adenomas – Pituitary Stalk compression (lack of dopamine) – Drugs- Antipsychotics (dopamine receptor antagonists like risperidone, phenothiazines, and haloperidol) Gastric motility drugs- Metoclopramide or domperidone High dose Estrogens PITUITARY HORMONE EXCESS- CORTICOTROPH & THYROTROPH ADENOMA Corticotroph adenoma causes Cushing’s Disease due to excess ACTH (There will be a separate lecture on this- Cushing’s Case Based Learning) Thyrotroph adenoma (rare): due to excess of TSH causes (central) hyperthyroidism GONADOTROPH ADENOMAS - PRESENTATIONS Excess in gonadotrophins secretion (FSH & LH) is very rare, and the symptoms are related to downstream upregulation. However clinically silent Pituitary adenomas often stain positive for Gonadotrophin histologically (SF 1 lineage ) but do not secrete (gonadotroph adenomas). In very rate situations when they secrete they can cause – Premature puberty in a boys, large testicles – Ovarian hyperstimulation in a premenopausal woman PITUITARY HORMONE DEFICIENCY Hypopituitarism is defined as a deficiency in one or more of the hormones normally secreted by the pituitary gland. If there is a deficiency in most or all of the hormones, it is termed panhypopituitarism. The most clinically relevant deficiencies are related to: Anterior: ACTH TSH FSH / LH Growth Hormone (GH) Posterior: Vasopressin (ADH) (will be taught later) PATHOPHYSIOLOGY OF PITUITARY HORMONE DEFICIENCY Tumours (Pituitary adenomas, cysts, metastatic cancer) – Causes damage by exerting pressure on pituitary cell – Pituitary macroadenomas are most commonly associated with hypopituitarism Pituitary surgery Radiation therapy (e.g.- brain tumor treated with radiation or pituitary radiation) Infiltration Hypophysitis (idiopathic or due to complication of immunotherapy used to treat cancer) Injury (e.g. traumatic brain injury, SAH, neurosurgery) Sheehan’s syndrome- ischemic necrosis of the pituitary secondary to hypotension from postpartum haemorrhage, resulting in panhypopituitarism HYPOTHALAMIC-PITUITARY HORMONAL DEFICIENCIES Growth Hormone – Short stature prior to epiphyseal closure – Decreased muscle mass, increased fat mass – Decreased bone mineral density Prolactin – Decreased lactation ACTH – Hypocortisolism TSH – Secondary Hypothyroidism LH, FSH – Hypogonadism PITUITARY HORMONE DEFICIENCY Deficiency of ACTH causes secondary adrenal insufficiency – The adrenal gland relies on the release of ACTH to control release of cortisol and also adrenal androgens. – The clinical presentation of this condition is almost exclusively as a result of cortisol deficiency. This allows us to distinguish it from primary adrenal failure (Addison’s Disease). – Can vary in degree from mild to life-threatening. Deficiency of TSH causes secondary hypothyroidism (refer to lecture on thyroid function and disease for symptoms and signs). Deficiency in gonadotrophins (FSH and LH) causes hypogonadotropic hypogonadism (secondary hypogonadism). GH deficiency causes short stature in Children, Non specific multitude of symptoms in adults ACTH DEFICIENCY Deficiency of ACTH causes secondary adrenal insufficiency. Symptoms usually nonspecific (which can delay diagnosis) ACTH DEFICIENCY – SIGNS & SYMPTOMS Symptoms: all caused by low Signs: all caused by low cortisol levels cortisol levels – Fatigue – Weight loss – disruption of – Anorexia/Nausea/Vomiting/ glucose homeostasis Abdominal pain – digestive – Hypoglycaemia – system dysregulation disruption of glucose – Myalgia / Arthralgia – homeostasis inflammation – Hyponatraemia – disruption – Amenorrhoea – disruption of fluid homeostasis of hormone regulation – Auricular cartilage – Psychiatric complaints – calcification (in men) – dysregulation of mood / disruption of calcium cognition homeostasis ADRENAL CRISIS A life-threatening complication of adrenal insufficiency. More common in primary adrenal insufficiency (Addison’s Disease) In secondary adrenal insufficiency, it is usually precipitated by – Insufficient glucocorticoid replacement ( non-compliance, non- adherence to sick day rules) during acute illness or – Acute secondary adrenal insufficiency such as pituitary apoplexy due to infarction or haemorrhage The main sign of adrenal crisis is cardiovascular collapse (shock) – hypotension, dehydration, coma, etc GONADOTROPHIN DEFICIENCY Deficiency in gonadotrophins (FSH & LH) causes hypogonadotropic hypogonadism (secondary hypogonadism). Symptoms: – Fatigue – Low libido, erectile dysfunction – Sweating, brain fog, loss of muscle mass, – Primary / secondary amenorrhoea (depending on age of onset) DEFICIENCIES – DIFFERENTIAL DIAGNOSIS Cortisol: Gonadotrophin: – Primary (Addison’s) / Secondary – Hypopituitarism adrenal insufficiency –Kallmann syndrome – Medications: Long term steroid –Constitutional delay use –Congenital disorders: e.g. T4: Prader-Willi – Primary hypothyroidism – Hypothalamic disorders – Secondary/Tertiary – Chronic illness (hypothalamic) hypothyroidism – Malnutrition GH: – Hypopituitarism – Syndromes: Prader-Willi, Turner, etc – Malnutrition – Chronic disease – Medications: long term steroids EXCESSES – DIFFERENTIAL DIAGNOSIS ACTH / Cortisol: Growth Hormone: – Pituitary adenoma (Cushing’s – Pituitary adenoma (Acromegaly) Disease) – Carney complex – Ectopic ACTH production: e.g. – McCune-Albright Syndrome SCLC – Adrenal adenoma/carcinoma Gonadotrophin: – Pituitary adenoma-very rare – Adrenal hyperplasia – PCOS – Exogenous cortisol: transplantation, chronic disease – Ovarian / testicular tumours (asthma, autoimmune disease, – Other hormone secreting tumours TSH / T3/ T4: – Pituitary adenoma – Graves’ disease – Toxic adenoma / multinodular goitre – Thyroiditis – Exogenous thyroid hormone use HORMONALLY-ACTIVE PITUITARY ADENOMAS : TREATMENT Prolactinomas: Medical therapy Dopamine agonists (Cabergoline, bromocriptine) Acromegaly: Pituitary surgery is primary therapy (Need expert surgeon!) Medical therapy (Somatostatin receptor ligands, GH receptor blocker) Radiation therapy is effective, but delayed onset Cushing’s: Pituitary surgery is primary therapy Medical Therapy (metyrapone, pasireotide, mifepristone, ketoconazole) if surgery is not possible or hypercortisolism is persistent after surgery Radiation therapy can be used in select older patients Bilateral adrenalectomy Response of Prolactinoma to Cabergoline BACK TO OUR CASE Cabergoline therapy initiated at 0.5mg weekly Prolactin levels normalized at 2 months Menses resume, galactorrhea resolves RESOURCES https://www.uptodate.com/contents/clinical-manifestations-of- hypopituitarism?search=hypopituitarism&source=search_result&selectedTitle=1~150&usage_type=default&display _rank=1 https://www.uptodate.com/contents/epidemiology-and-clinical-manifestations-of-cushing- syndrome?search=cushing%20syndrome&source=search_result&selectedTitle=3~150&usage_type=default&displ ay_rank=3 https://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-hyperthyroidism-in- adults?search=hyperthyroidism&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 https://www.uptodate.com/contents/clinical-manifestations-of-adrenal-insufficiency-in- adults?search=secondary%20adrenal%20insufficiency&topicRef=173&source=see_link https://www.uptodate.com/contents/clinical-manifestations-of- hypothyroidism?search=hypothyroidism&source=search_result&selectedTitle=3~150&usage_type=default&display _rank=3 https://www.uptodate.com/contents/arginine-vasopressin-deficiency-central-diabetes-insipidus-clinical- manifestations-and- causes?search=diabetes%20insipidus&source=search_result&selectedTitle=1~150&usage_type=default&display_ rank=1 https://www.uptodate.com/contents/pathophysiology-and-etiology-of-the-syndrome-of-inappropriate-antidiuretic- hormone-secretion- siadh?search=SIADH&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 https://www.uptodate.com/contents/causes-and-clinical-manifestations-of- acromegaly?search=acromegaly&source=search_result&selectedTitle=2~88&usage_type=default&display_rank=2 #topicGraphics