Alterations of the Endocrine System

Describe names, location and hormones secreted by endocrine glands and their function (review).

Describe three ways target cells fail to respond to hormones, creating hormonal dysfunction.

Compare the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and diabetes insipidus in regards to: causative factors, pathophysiology, manifestations, treatment, and prognosis.

Describe the causes and clinical manifestations of hyper- and hypopituitarism.

Describe the manifestations and consequences of pituitary adenomas and prolactinomas.

Describe the progression of hyperthyroidism through Graves disease and thyroid storm in relation to cellular changes, manifestations, treatments and complications.

Describe the causes, and outcomes for disorders that produce hypothyroidism.

Differentiate between primary and secondary hyperparathyroidism.

Describe the similarities and differences in the onset, etiology and pathophysiology of type 1 and type 2 diabetes mellitus.

Describe the acute and chronic complications of diabetes mellitus.

Compare hypercortical function (Cushing disease and syndrome) and hypocortical function (Addison disease) including causative factors, pathophysiology, manifestations, treatment and prognosis.

Describe common tumors of the adrenal medulla.

The Reproductive System

Describe the normal structure and function of the reproductive system (review).

Define alterations of sexual maturation.

Describe types, manifestations of menstrual alterations.

Describe pelvic relaxation disorders.

Describe benign growths and proliferative conditions of reproductive tract.

Discuss main features and impact of infertility.

Describe selected disorders of the prostate gland.

Describe briefly male and female sexual dysfunction.

Describe briefly benign and malignant breast lesions.

Endocrine System: Anatomy and Physiology Review

Endocrine glands

Hypothalamus

– Secretes releasing hormones (RH) which in turn stimulates hormone release from the anterior pituitary

– Hormones secreted by the hypothalamus: GHRH, TRH, CTH, GnRH, Dopamine (PIH), MSH IH

o Note: Dopamine and MSH IH are inhibiting hormones

Pituitary

– Anterior and posterior lobes

– Anterior lobe secretes hormones in response to the releasing hormones from hypothalamus

o Anterior hormones: GH, TSH, ACTH, FSH, LH, Prolactin, MSH

– Posterior lobe secretes hormones in direct response to neuronal signals from the hypothalamus. *No releasing hormone*

o Posterior pituitary hormones: ADH, Oxytocin

Thymus = immune tolerance

Thyroid

Adrenal gland

Pancreas = endocrine and exocrine

Gonads

Note: There are some endocrine cells in the kidney as part of the juxtaglomerular apparatus (JGA). These cells release renin and erythropoietin hormones

– Renin stimulates mechanisms to regulate blood pressure

– Erythropoietin stimulates red blood cell formation

Regulation of Calcium

There are 3 hormones responsible for the regulation of calcium

– Parathyroid hormone

o Breaks down bone to increase blood calcium

– Calcitriol (active Vit D = D3 = 1,25 cholecalciferol)

o Stimulated calcium absorption in intestine

– Calcitonin

o Inhibits bone resorption to decrease blood calcium

Urine Analysis

Urine may contain small amounts of glucose, urobilirubin and protein

Urine has NO bacteria, yeast, ketones, nitrates, leukocytes, bilirubin

Urine may have crystals occasionally

If hypovolemic, the osmolarity (amount of solutes per solvent) increases

– This may be observed as more concentrated, darker urine

– The person may also have decreased output relative to normal

Etiology of endocrine disorders

Primary:

Pathologies within endocrine organs

Congenital, inflammatory, metabolic, immune, malignancy (tumor)

Secondary:

Pathologies outside the primary endocrine organs (in the controlling gland)

Secondary pathologies can stem from the following mechanisms:

– Hypothalamus or pituitary gland (these are the controlling glands)

– Target cell/tissue

o Non-responsive (receptor associated issues)

• Low number of receptors

• Impaired receptor function

• Antibodies against receptors

Endocrine Disorders -Basics

Types

Hyperfunction: elevated hormone levels

Hypofunction: decreased hormone levels

Etiology/malfunction

– Reduced or excess synthesis

– Failure of feedback mechanisms

– Excessive degradation

– Inactivation or hyperstimulation by antibodies

– Ectopic hormone secretion

Alterations of the Hypothalamic-Pituitary axis

Note: RH = releasing hormone; IH/IF = inhibiting hormone

Dopamine (referred to in Figure 7 as PIH [prolactin inhibiting hormone]) and MIH (melanocyte inhibiting hormone) act to decrease hormone production opposite to releasing hormones

– Therefore, decreased production of inhibiting hormone would increase hormone production/release from the pituitary

– Example: Dopamine as an Inhibiting Hormone

o Decreased production of dopamine (PIH) leads to increased prolactin levels

Hypopituitarism

Decreased function of the pituitary

Can be from inadequate levels of hypothalamic hormones

Defects in pituitary gland itself

Causes

Invasive, space occupying lesion (Tumor or aneurysm)

Infections: (TB, syphilis, meningitis)

– TB encephalitis is rare, but it can occur to the pituitary

Trauma (severe head trauma)

Autoimmune disease

– Leads to destruction of the gland

Sheehan syndrome (postpartum pituitary infarction that leads to necrosis)

– Postpartum bleeding leads to ischemia and can lead to subsequent ischemic damage to the pituitary

Pathophysiology

Inflammation, ischemic necrosis, infarction, fibrosis

Edema and swelling of the pituitary within the sella turcica further impede blood supply to the gland causing further shrinkage and fibrosis

Clinical manifestations

Could see symptoms related to specific hormone deficiency (e.g. FSH, LH, ACTH)

Diagnosis

Diagnosis is often challenging

Triple bolus test = insulin + TRH + GnRH and then assess. You should see hypoglycemia, elevated TSH and elevated FSH and LH. If you don’t see this = pituitary issue

CT scan can view the gland for trauma or tumor

Laboratory results need to be interpreted in conjunction with/or in light of clinical manifestations

Prolactinoma (hyperpituitarism)

The most common pituitary tumor

Benign, hyperfunctioning, slow-growing pituitary adenoma

Pathophysiology:

Mass secreting prolactin

Sustained elevation of serum prolactin

Compression effects from tumor mass (e.g. visual disturbances)

Clinical manifestations

Compression effects: optic chiasm; visual impairment, headache

Functional effects:

– Female: amenorrhea, galactorrhea, hirsutism, infertility, osteopenia

– Male: gynecomastia, erectile dysfunction

Treatment

Medication: Dopamine agonists

Since the tumor secretes prolactin, dopamine (which has the same chemical structure as PIH) can be used to decrease and maintain prolactin levels PIH is the same as dopamine in structure

Dopamine drugs can be used to inhibit synthesis of prolactin in remaining tumor mass following surgery

Surgical approach: removal of the tumor

Diabetes Insipidus (DI)

The inability to retain water leading to excessive diuresis evidence by urination

Central (Neurogenic) DI

No ADH secretion

Excessive diuresis due to failed ADH synthesis/release

Potential causes include:

– Idiopathic, head trauma, tumors, vascular, autoimmune, infection, drugs and surgery

Nephrogenic DI

Renal resistance to ADH

– ADH is made, but is not working in the kidney

May be related to disease or drugs

Pathophysiology:

Failure of ADH action on the distal convoluted tubule (DCT) and collecting ducts

Inability to concentrate urine

Clinical manifestations

Polyuria, polydipsia, Nocturia

test

– Patient is not given water

– The ADH level should increase with a decrease the frequency and amount of urination

DDAVP (synthetic ADH) test

– Patient gets synthetic ADH

– If there is no change in urine concentration, then it confirms a nephrogenic DI

Syndrome of Inappropriate ADH secretion (SIADH)

Water retention due to ADH hypersecretion

– Decreased urine output and/or concentrated urine

Etiology:

Ectopic (paraneoplastic syndrome; GI, bladder, prostate)

– Usually a tumor somewhere that is secreting ADH

CNS disorders: stroke, infection, tumors

Pathophysiology

Enhance renal water retention

Dilutional hyponatremia, plasma hypo-osmolarity

Concentrated urine

Clinical manifestations

Patient will present with symptoms of hyponatremia. E.g. Confusion, delirium, muscle weakness, seizures, coma

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