Pituitary and Adrenal Disease

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Pituitary and Adrenal Disease

• Anne Marie Van Hoven, M.D.

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Anatomy of the Pituitary Gland
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Pituitary Hormones

• Anterior Pituitary
• Thyroid Stimulating Hormone (TSH)
• Adrenocorcticotropic Hormone (ACTH)
• Growth Hormone (GH)
• Follicle Stimulating Hormone (FSH)
• Luteinizing Hormone (LH)
• Prolactin (Prl)
• Posterior Pituitary
• Arginine Vasopressin (AVP)
• Oxytocin

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Hypothalamic Hormones

• Thyrotropin Releasing Hormone (TRH)
• Corticotropin Releasing Hormone (CRH)
• Growth Hormone-Releasing Hormone (GHRH)
• Growth Hormone Release Inhibiting Hormone
  (Somatostatin)
• Gonadotropin Releasing Hormone (GnRH)
• Prolactin Release Inhibiting Hormone (Dopamine)

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The Hypothalamic- Pituitary Axes
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Lesions of Hypothalamic Pituitary Axis

• Hypothalamic (hypothalamic or pituitary stalk
  disease) vs. Primary Pituitary Disease
• Acquired Defects Tumors (inc. Pit. Adenomas),
  Trauma, Irradiation, Inflammatory/Infiltrative
  d/s, Vascular d/s (inc. Apoplexy), Empty Sella,
  Primary Neoplastic d/s, Metastatic d/s,
  Metabolic d/s and Functional d/s.
• Congenital Embryopathic Defects Kallmans
  syndrome, Pituitary Aplasia, Anencephaly, Midline
  defects.
• Genetic Defects Hypothalamic / Pituitary Hormone
  Gene Defects and Hormone Receptor Gene Defects.

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Clinical Manifestations of Lesions of
Hypothalamic Pituitary Axis

• Mass effects Headaches, Visual Field and CN
  III-VI Defects, Obstructive Hydrocephalus, CSF
  Rhinorrhea, Hypothalamic Syndromes (DI, SIADH,
  thirst/ appetite/ satiety/ sleep/ temperature
  regulation), Frontal/ Temporal Lobe Dysfunction
• Endocrine Effects
• Hypopituitarism TSH/ ACTH/ GH/ LH-FSH/ Prolactin
• Hyperpituitarism TSH/ ACTH/ GH/ LH-FSH/ Prolactin

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Mass Effects of Pituitary Lesions
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Organization of visual fibers at the Optic Chiasm
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Pre- And Postoperative Visual Fields
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Pituitary Adenoma With Involvement Of Left
Oculomotor Nerve
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Pituitary Tumor
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Pituitary Apoplexy
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Pituitary Apoplexy w/ OC compression
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Clinical Manifestations of Lesions of
Hypothalamic Pituitary Axis

• Mass effects Headaches, Visual Field and CN
  III-VI Defects, Obstructive Hydrocephalus, CSF
  Rhinorrhea, Hypothalamic Syndromes (DI, SIADH,
  thirst/ appetite/ satiety/ sleep/ temperature
  regulation), Frontal/ Temporal Lobe Dysfunction
• Endocrine Effects
• Hypopituitarism TSH/ ACTH/ GH/ LH-FSH/ Prolactin
• Hyperpituitarism TSH/ ACTH/ GH/ LH-FSH/ Prolactin

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Syndrome of Panhypopituitarism

• Progressive loss of Anterior Pituitary function
  FSH/LH and GH TSH ACTH.
• Hypopituitarism with DI is suggestive of
  Hypothalamic etiology.

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Syndrome of Panhypopituitarism
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Control of Gonadotropin Secretion
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Syndrome of Panhypopituitarism

• FSH / LH deficiency
• In women Oligo-amenorrhea, Infertility,
  Post-menopausal symptomatology, Bone loss.
• In Men Decreased Libido, ED, Gynecomastia with
  loss of secondary sexual characteristics, Bone
  loss.
• Labs Gonadotropins inappropriately low for E2 in
  women and T in men.

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Syndrome of Panhypopituitarism

• GH deficiency in Adults
• Symptoms Reduced muscle mass and decreased
  exercise performance, Increased abdominal
  adiposity, Decreased psychosocial well being.
• Signs Central adiposity, thin dry skin,
  Decreased muscle strength.
• Labs Hyperinsulinemia, Dyslipidemia,
  Low-normal IGF-1 with inadequate response on
  Insulin tolerance test/ L-Dopa test/ L-Arginine
  test.

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Syndrome of Panhypopituitarism

• GH deficiency in Children
• GH deficiency (especially prior to onset of
  puberty) leads to growth retardation/ short
  stature.
• Thyroid and Corticosteroid replacement are
  necessary for GH action in patients with
  panhypopituitarism.

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Syndrome of Panhypopituitarism

• TSH deficiency
• Symptoms Fatigue, Cold intolerance, Lethargy,
  Constipation, Diminished appetite, Weight gain,
  Hoarseness of voice, Menorrhagia.
• Signs Bradycardia, Hypothermia, Pale/ cool/ dry
  skin, dry hair, hung up DTRs, stupor/ coma in
  severe cases.
• Labs Low-normal TSH with low Free T4, Abnormal
  TRH Stimulation test, Hyponatremia in severe
  cases.

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Syndrome of Panhypopituitarism

• ACTH deficiency
• Symptoms Weakness, Fatigue, Nausea/ Vomiting,
  Weight loss
• Signs Pale skin with inability to tan, Postural
  Hypotension.
• Labs Mineralocorticoid function is preserved,
  Low AM cortisol, /- ACTH Stimulation test, Poor
  pituitary ACTH reserve on Insulin tolerance test/
  CRH stimulation test/ Metyrapone test.

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Maintenance Medications for Hypopituitarism
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Empty Sella Syndrome

• Defects in diaphragma sella allowing herniation
  of arachnoid membrane into the hypophyseal fossa
  thereby leading to transmission of ICP and
  compressing the pituitary against the walls of
  the sella.
• Primary vs. Acquired (Surgery, Radiation therapy,
  Infarction)
• Pituitary function is usually normal /- mild
  elevations of Prolactin.

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Empty Sella Syndrome
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Clinical Manifestations of Lesions of
Hypothalamic Pituitary Axis

• Mass effects Headaches, Visual Field and CN
  III-VI Defects, Obstructive Hydrocephalus, CSF
  Rhinorrhea, Hypothalamic Syndromes (DI, SIADH,
  thirst/ appetite/ satiety/ sleep/ temperature
  regulation), Frontal/ Temporal Lobe Dysfunction
• Endocrine Effects
• Hypopituitarism TSH/ ACTH/ GH/ LH-FSH/ Prolactin
• Hyperpituitarism TSH/ ACTH/ GH/ LH-FSH/ Prolactin

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Pituitary Adenoma

• Microadenomas are lt 10mm.
• Macroadenomas are 10mm.
• Majority are monoclonal and not malignant.
• May or may not be functional.
• Mass effects and hypopituitarism may be present
  irrespective of functional status.

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Prevalence of Pituitary Adenomas
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The Thyroid Axis
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TSH secreting Pituitary Adenoma

• TSH molecule may be biologically inactive or may
  cause clinical hyperthyroidism resembling Graves
  disease.
• TSH levels are variable, from normal to as high
  as 500s.
• Diagnosis Inappropriately elevated TSH in
  presence of high T3/T4 is highly suggestive.
  Alpha Subunit levels may be significantly
  elevated.
• Treatment Pituitary Surgery, Radiation therapy,
  Octreotide, Anti-thyroid drugs and RAI.

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Prevalence of Pituitary Adenomas
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GnRH pulses induce secretory pulses of
luteinizing hormone LH
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FSH/LH secreting Pituitary Adenoma

• No characteristic syndrome of hormone excess is
  seen.
• Occasionally-
• In Men /- testicular enlargement, hypogonadal
  symptoms.
• In Women /- hypogonadal signs and symptoms.
• Treatment Pituitary surgery, Radiation therapy.

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Prevalence of Pituitary Adenomas
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Neuroendocrine regulation of the HPA axis
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ACTH secreting Pituitary Adenoma(Cushings
Disease)

• Accounts for about 60-70 of cases of Cushings
  syndrome.
• Symptoms Fatigue, Weight gain, Easy bruising,
  Headaches, Irregular menses, Psychiatric symptoms
  from depression to frank psychosis.
• Signs Plethoric Moon facies, Buffalo hump,
  Central adiposity with thin extremities,
  Hyperpigmentation, Hypertension, Hirsuitism,
  Acne, Purple striae, Proximal myopathy.

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ACTH secreting Pituitary Adenoma(Cushings
Disease)

• Labs IFG/IGT, Hypokalemia and Alkalosis,
  Leukocytosis, Lymphopenia, Bone loss on DXA.
• Diagnosis Elevated 24 hour urinary free
  cortisol and/or lack of suppression by low dose
  dexamethasone, Elevated ACTH levels, Ectopic ACTH
  syndrome ruled out.
• Treatment Pituitary surgery, Medical therapy as
  temporizing measure, Radiation therapy, Bilateral
  Adrenalectomy (with 10-50 risk of Nelsons
  syndrome)

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Prevalence of Pituitary Adenomas
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GH secreting Pituitary Adenoma(Acromegaly)

• Acral and facial growth in Adults (once the
  epiphyses of long bones are fused).
• 40 may co-secrete Prolactin.
• Symptoms Headaches, Arthralgias, Fatigue,
  Hyperhidrosis, entrapment neuropathies, Sleep
  Apnea, Deepening of voice, Impotence in men,
  irregular menses in women.

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GH secreting Pituitary Adenoma(Acromegaly and
Gigantism)

• Signs Coarsening of facial features, enlarged
  hands and feet, oral malocclusion and increased
  spacing between teeth, Moist doughy skin,
  increased heel pad thickness, Hypertension,
  Goiter.
• Labs IFG/IGT, /- elevated Prolactin,
  Hypogonadism.
• Diagnosis Elevated IGF-1, Abnormal GTT.

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Management of Acromegaly
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Prevalence of Pituitary Adenomas
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Causes of Hyperprolactinemia
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Prolactin secreting Pituitary Adenoma

• Most common Pituitary lesion.
• Majority are microprolactinomas, few are
  macroprolactinomas.
• E2 stimulates lactotroph proliferation.
• Note Physiologic elevation of Prolactin is seen
  in pregnancy.
• Idiopathic Prolactinoma When the etiology is
  unclear. A subset of these patients may have
  macroprolactinemia.

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Prolactin secreting Pituitary Adenoma

• Prolactin gt200ng/ml is consistent with
  Prolactinoma
• Prolactin lt50ng/ml is often secondary to
  physiologic causes.
• Prolactin 20-100ng/ml may be secondary to
  pituitary stalk compression by tumors not
  actively secreting Prolactin.

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Prolactin secreting Pituitary Adenoma

• Clinical Presentation Signs and Symptoms of
  hypogonadism (especially amenorrhea and
  infertility in pre-menopausal women) /-
  galactorrhea (especially in women) and
  gynecomastia (in men) /- tumor mass effects.
• Diagnosis Elevated Prolactin levels in the
  presence of Pituitary lesion on imaging and other
  causes of Hyperprolactinemia ruled out.

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Management of Prolactinoma
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Transsphenoidal Surgical Approach
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Morbidity and Mortality in Transsphenoidal
Surgery
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Posterior Pituitary and AVP Secretion
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Variables influencing Plasma AVP

• Osmotic Plasma Osmolality (Water balance)
• Hemodynamic Volume and Pressure sensing
• Others Emesis, Hypoglycemia

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Diabetes Insipidus

• Excretion of a large volume (usually gt4 L/d) of
  hypotonic urine in absence of glycosuria.
• Differential Diagnosis
• Hypothalamic/ Central DI
• Nephrogenic DI
• Primary Polydipsia
• Serum Sodium is usually maintained in the normal
  range. Diagnosis is suggested by inappropriately
  low Urine Osmolality in relation to the Serum
  Osmolality.

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Causes of Diabetes Insipidus
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Diabetes Insipidus

• Clinical Features
• Central DI Relatively abrupt onset of symptoms,
  Preference for cold liquids, Polyuria and Thirst
  persisting through the night.
• Nephrogenic DI Lithium, Demeclocycline use,
  Hypokalemia, Hypercalcemia.
• Psychogenic Polydipsia Erratic course,
  Symptoms exacerbated during stress, Minimal
  disruption of sleep (lack of nocturia),
  Underlying psychiatric disease.

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Treatment of DI

• Adequate water replacement is essential to avoid
  metabolic complications.
• Central DI DDAVP (Selective action on
  antidiuretic V2 receptors, minimal on pressor V1
  receptors)
• Nephrogenic DI Thiazide leading to greater
  proximal tubular reabsorption of glomerular
  filtrate.

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SIADH

• Hyponatremia with low plasma osm
• Urine less than maximally dilute
• Increased urine sodium
• Euvolemia
• Normal thyroid and adrenal fxn
• No drugs that increase ADH

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Adrenal Diseases

• Cushings Syndrome
• Addisons Disease
• Conns (primary hyperaldo)
• Pheochromocytoma

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Adrenal Gland
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Hormone Synthesis
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Cushings Syndrome
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Cushings Signs and Symptoms

• Moon facies
• Buffalo hump
• Purple striae
• Hypertension
• Proximal muscle weakness
• Central obesity

• Acne
• Easy Bruisability
• Gonadal dysfxn
• Hirsutism
• Osteopenia

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Work up for Cushings

• 24 hour urine free cortisol
• Morning and afternoon cortisol
• Low dose dexamethasone suppression test
• High dose dexa supp test

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Treatment

• Surgery
• Radiation
• Medical - ketoconazole

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Addisons Disease etiologies

• Autoimmune (75)
• Metastasis lung, breast
• Hemorrhage anti coagulant, Waterhouse-Friderichs
  en, trauma
• Infectious (TB, CMV, Histo)
• HIV
• amyloidosis

• Hemachromatosis
• Adrenal Hypoplasia
• Drugs ketoconazole, metyrapone, phenytoin,
  barbiturates, rifampin

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Signs and symptoms

• Hyperpigmentation
• Hyponatremia
• Hyperkalemia
• Hypotension
• Hypoglycemia
• Postural sx
• Weakness/fatigue
• Vitiligo
• Eosinophilia
• Hypercalcemia

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Work up

• Am Cortisol
• ACTH stimulation test
• Use ACTH level to distinguish primary from
  secondary

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Treatment

• Hydrocortisone or any steroid replacement
• IV Fluids if is hypotension is a concern
• Mineralocorticoid if secondary (fludrocortisone)

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Endocrine Hypertension
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Actions of Aldosterone

• Increase Na resorption, increase volume, increase
  blood pressure
• Increase K excretion
• Decrease renin activity by negative feedback
• Decreased K means hydrogen moves into the cells
  which leads to metabolic alkalosis

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Conns Syndrome Primary Hyperaldosteronism

• One etiology of Endocrine Hypertension
• Consider in setting of HTN, hypokalemia
• Due to adenoma, bilateral adrenal hyperplasia or
  carcinoma

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Work Up

• Random Renin if normal or high, its not
  hyperaldo
• High salt diet with patient upright for 4 hours
  measure plasma aldo and renin. Aldorenin gt25
  suggests dx (caveat is that aldo needs to be
  high)
• Saline suppression- Plasma aldo level before and
  after 2L normal saline bolus
• Captopril test

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Dx and Rx

• CT imaging
• Venous sampling
• Surgery
• Spironolactone

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Pheochromocytoma

• Paroxysmal
• HTN
• HA
• Sweating
• Palpitations
• Anxiety
• N/V
• fatigue

• Visual disturbances
• Facial pallor or flushing
• Cold hands/feet
• hyperglycemia

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Dx and Rx

• 24 hour urine for VMA, metanephrine
• Localize tumor by CT scan, MRI or MIBG
• Rx Alpha blockade, Beta blockade in preparation
  for surgery

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MEN

• MEN Type I
• parathyroid tumors
• pituitary tumors
• pancreatic tumors
• MEN Type IIa
• medullary thyroid carcinoma
• pheochromocytoma
• hyperparathyroidism
• MEN Type IIb
• medullary thyroid carcinoma
• pheochromocytoma
• mucosal neuromas

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The End