Pituitary Gland

 

Pituitary gland

PKGhatak, MD

The pituitary gland is a small endocrine gland, located at the base of the skull in the middle fossa and sits in the Sella turcica (Turkish saddle) of the sphenoid bone. The roof of the nose is just below it and is separated by a thin perforated bone partition called cribriform plate, the hypothalamus and optic chiasma are located just above the pituitary gland. The pituitary is positioned in between the eyes when projected on the surface. The pituitary is connected with the hypothalamus by a stalk consisting of nerve fibers and blood vessels, The frontal cortex overhangs in front of the pituitary.

The pituitary gland is two glands in one structure - the anterior pituitary and posterior pituitary. Both parts are endocrine in nature. The posterior pituitary is an extension of the hypothalamus. In between the two pituitaries are cells that form pars intermedia.

Embryology of Pituitary.

The ectoderm cells of the developing roof of the mouth grow upwards in the form of a pouch-Rathke's pouch. The neurons from the floor of the 3^rd ventricle of the brain extend down as an outgrowth to meet Rathke's pouch. These two sources make up the Pituitary gland – the anterior pituitary (adenohypophysis) originates from the cells of the roof of the mouth, the posterior pituitary (neurohypophysis) from the extension of the brain. The line of junction of these two parts contains cells and is known as Pars Intermedia. Pars intermedia is ultimately incorporated in the anterior pituitary and these cells produce MSH - melanocyte stimulating hormone. 

The pituitary gland is the conductor of an endocrine orchestra. The orchestra players are the adrenal glands, thyroid, thymus, pancreas, pineal, and testis/ovaries. The nerve center of this orchestra is the hypothalamus. Hypothalamus with its nerve fibers and the portal circulatory system sends signals to both pituitary glands. Hypothalamus is the headquarters of the autonomic nervous system. Hypothalamus acts as a bridge between the CNS and endocrine systems 

Special Three:

The pituitary, hypothalamus and pineal have a closer relationship. The pineal gland produces melatonin, a hormone and through melatonin, the pineal maintains the circadian cycle, sleep, and waking rhythm. The pineal gland is considered the spiritual center and so called the 3^rd eye. These three structures (Pituitary, hypothalamus and pineal gland) working together are responsible for the control of heart rate, BP, apatite, body temperature, respiration, emotion and behavior, sexuality and fertility, growth, of bones & muscles. skin color, water & electrolyte balance and health.

Hypothalamus communicates with the anterior pituitary by releasing hormones. Every anterior pituitary hormone is produced by a separate cell line; so, the hypothalamus has multiple releasing hormones.              Examples- ACTRH (adrenocorticotropic releasing hormone), TSRH,GHRH, etc. The nerve fibers from the hypothalamus send signals to release preformed hormones - ADH (antidiuretic hormone) and Oxytocin.

The hormone secretion from the pituitary gland is not continuous. Every 2 to 3 hours hormones are released in circulation.

Hormones of Anterior Pituitary:

Anterior pituitary gland hormones are ACTH (adrenocortical stimulating hormone).

 TSH (thyroid stimulating hormones).

 Gonadotropins- LH (luteinizing hormone), FSH (follicle stimulating hormone).

 MSH (Melanocyte stimulating hormone).

Posterior Pituitary hormones are. ADH (antidiuretic hormone) and Oxytocin.

ADH is produced by neurons of the hypothalamus and travels down the nerve fibers to the posterior pituitary and is stored in the vesicles. With the appropriate signal from the hypothalamus, ADH is secreted.

Oxytocin. Oxytocin is likewise produced by neurons of the posterior pituitary, travels to the posterior pituitary like ADH.

The pituitary gland may overproduce or fail to produce adequate quantities of the hormone. It also may develop tumors. Benign tumors of the anterior pituitary are the majority of tumors.

Table of Pituitary hormones.

Hormone	Target organ	Excess production	Deficiency
GH- growth hormone	Bones and muscular system.	Gigantism in children, Acromegaly in adults.	Dwarfism, Growth retardation. Osteoporosis, muscular weakness, depression.
ACTH	Adrenal cortex	Cushing disease	Addison's disease
TSH- thyroid stimulating hormone	Thyroid gland	Hyperthyroidism	Hypothyroidism
Gonadotropin LH- luteinizing hormone	Germ cells of Ovaries/testicles		Failure to conceive if female. Low sperm count in males.
Gonadotropin FSH- follicle stimulating hormone	Interstitial cells of ovaries/testicles	Many adverse effects on estrogen excess and hyper testosterone, Blood clots to increase hepatic and other tumors.	Few and scanty menstruation to amenorrhea in females. Erectile disorder in male.
Prolactin	Breast both sexes	Lactation without pregnancy. Milk secretion in male	Lactation deficiency in post partem..
MSH- melanocyte stimulating hormone	Melanocytes of skin	Production of pigments of skin and hair	Vitiligo and albinism
ADH- antidiuretic hormone	Kidney tubules	Fluid overload and hyponatremia	Dehydration and inappropriate production of dilute urine
Oxytocin	Pregnant Uterus	Rupture uterus	Failure of placental separation and poor uterine contraction during labor.

A few special Pituitary disorders.

Chromophobe Adenomas of Pituitary. Chromophobe adenoma of the pituitary is the most common adenoma and is a benign tumor. Pituitary adenoma does not secrete any hormone. and cells contain no granules, however, under the electron microscope, a few granules are detected. Symptoms of adenoma are related to increased internal pressure and hypofunction of the pituitary but symptoms vary because all different cell lines are not equally affected. Often the prolactin levels are high and ACTH, TSH and GH are lower.

MENS 1. Multiple endocrine neoplasia type one. Tumors of the anterior pituitary (mostly of prolactin producing cells) arise in association with tumors of parathyroid glands, pancreatic tumors – insulinomas and glucagonomas, and tumors of small intestinal hormone producing cells. The disease is inherited in an autosomal dominant pattern. Additional tumors of the adrenal gland, carcinoids, angiofibroma and meningiomas may be associated.

Sheehan syndrome. Massive postpartum bleeding leads to shock and pituitary necrosis. If patients survive the shock, then hypothyroidism, adrenal insufficiency, and menopause develop.

Empty Sella syndrome. The pituitary sits in a bony cup, only the top is covered by soft tissues. In benign intracranial hypertension, the persistent high CSF pressure produces gradual atrophy of the pituitary and symptoms of hypopituitarism develop.

Prolactinoma. Tumors of prolactin producing cells are either microscopic tumors or macroscopic large tumors- both are benign. Excess prolactin is associated with a deficiency of other anterior pituitary hormones. Symptoms of low cortisol and hypothyroidism are most manifested initially. Macrotumors produce increased CSF pressures, visual field defects, and eye muscles palsy in addition to hormonal changes.

Nelson syndrome. Following bilateral adrenal gland removal in Addison syndrome, the cells producing ACTH in the pituitary grow in excess and forms tumor. Besides Cushnoid features, various visual symptoms and blindness may develop.

Craniopharyngioma. Craniopharyngiomas are benign cysts and occasionally solid adenoma developed from the remnant cells of Rathke's pouch. Symptoms are increased intracranial pressure and visual field defects. This entity is a childhood malady and is occasionally seen in adults.

Rathkes cleft cysts. Cysts develop in the remnant Rathkes pouch. The presentation is very similar to craniopharyngioma.

Lymphocytic hypophysitis. This entity is a rare complication seen in late pregnancy or early postpartum. It is an autoimmune disease with lymphocytic infiltration of the pituitary gland and results in various degrees of hypofunction of the pituitary. The cause is unknown, IgG4 and IgG1 antibodies were detected by some investigators pointing to heterogenic sources of antigen.

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Appendix

 

Appendix

PKGhatak, MD

Appendix means an attachment to a document. Centuries earlier when Geeks began to dissect cadavers to study human anatomy, they described a small narrow tube hanging from the cecum and called it an appendix. Appendix later received a nastier name in 1579 given by Yolanda Smith - Vermiform appendix (worm like appendix) and that name got tucked in the medical field.

 ..Before the days of general anesthesia and sterilization, infection of the appendix was bad news as bad as a death sentence. In 1735 Dr. Claudius Amyland in London, England successfully surgically removed an appendix from an 11 yr. boy who had swallowed a needle that perforated his appendix and lodged in the scrotum.

..In the Journal of Evolution Biology H.F Smith et al described that Appendix evolved twice in the animal kingdom, the latest appearance was in marsupials. The appendix has largely disappeared from the animal kingdom and now the appendix is found only in humans, primates, rabbits, prehensile tailed porcupines, flying squirrels, meadow voles and wombats.

..There are wide variations in the anatomy of the cecum and appendix in mammals – some have only multi chambered cecum and appendix and no small bowels, some have a larger appendix and small cecum, and some only appendix and no cecum.

..Human appendix in adults is about 3 inches long, attached to the far end of the cecum next to the junction of the small intestine to the cecum. The appendix is richly supplied by arterial blood. The size of the appendix is much larger in the developing fetus and continues to grow through early childhood and starts to diminish in size with the onset of sex hormones secretion.

..A microscopic look at the appendix will convince anyone that the appendix belongs to the lymphatic system. The lymph follicles of the appendix are large compared to the rest of the tissues, the follicles are many and arranged in a circle. Structurally the appendicular lymph follicles resemble Peyer's patches of the small intestine and functionally perform like the thymus gland. In fact, calling the appendix the intestinal thymus is not that far off.

In the appendix, lymph follicles contain lymphocyte B-cells and T-cells. B-cells and T-cells communicate with each other and function like T & B-cells in any other tissue. The bacterial antigen and other antigens are identified and collected by T-cells then given to B-cells. Cytokines of T-cells act on lymph follicles and produce immunoglobulin IgA. IgA is the immunological defense of the GI tract and prevents the invasion of bacteria, fungi, viruses, and toxins. IgA is also produced in the lymphatic tissues of the rest of the intestine.

.. Besides immunological functions, the appendix is the home of beneficial bacteria in the large gut. When diarrheal diseases and the use of antibiotics wipe away the gut bacteria and the overgrowth of harmful bacterial produce illness, the appendix replenishes new batches of beneficial bacteria.

..In reconstructive surgery, the appendix is utilized and fashioned as a sphincter of a newly created urinary bladder out of a section of the gut and also use appendix as the replacement part of a removed ureter.

..In earlier days the appendix of ruminant animals was considered a storehouse of fermenting bacteria and that belief led Charles Darwin to consider the human appendix as a relic of leaf-eating humans.

..The incidence of appendicitis is about 1 million a year in the USA. The mortality rate is 0.3%. Present days the diagnosis of acute appendicitis is made easier by Ultrasound studies. A swollen appendix and local peritoneal ascites (fluid collection) mean acute appendicitis. In retrocecal appendicitis or in ectopic pregnancy an MRI is referable. Elucidating one finger tenderness at the McBurney and leukocytosis with a left shift are not solely relied upon, but are important clinical findings.

A recent trend in appendicitis treatment is the use of antibiotics alone, no surgery, and careful watch provided ultrasound study does not show fluid collection.

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Color of Urine.

 

Color of Urine

PKGhatak, MD

The normal color of urine is pale yellow. The hemoglobin breakdown product bilirubin is excreted by the liver in the bile. Most of the bilirubin is eliminated from the body in the stool, some 20 % is reabsorbed and filtered by the kidneys. In the urine it appears an urobilirubin and that colors the urine.

..Dehydration produces dark yellow color urine; pale urine is produced from drinking several glasses of beer. Urine color becomes barely noticeable or absent in common bile duct obstruction from impacted gall stones or pancreatic cancer.

..Consuming beetroot, carrots, and blackberries, make urine red and various shades of yellow. Green urine is likewise seen after eating asparagus. In the summer months eating ice shavings with colored syrup and colored ice cream can give a variety of colored urine.

..People taking prescription medications, if they read the printed information given by the pharmacy, will find certain pills may discolor the urine.

 Drugs producing colored urine: -

..Orange color – Rifampin and other Rifampin derivatives, Sulfadiazine, Senna. Warfarin, Phenazopyridine.

..Pink color – Phenolphthalein, Vitamin B12, Senna.

..Brown color – Nitrofurantoin, Metronidazole, chloroquine.

 .Black color – Sorbitol, Methyldopa.

..Blue color – IV methylene blue. Indigo carmine.

..Green color – Promethazine, cimetidine, Amitriptyline, Indocin, Metoclopramide.

 Diseases producing colored urine: - Red urine. - Bleeding from the urinary bladder, kidneys and urinary tract due to stones, tumors, tuberculosis and trauma including surgery.

..Brown urine. - Free hemoglobin and myoglobin (hemoglobin of skeletal muscles) in the urine. This may arise from crush injuries, Rhabdomyolysis. Prolonged march. Electric shock, Seizures. Massive pulmonary infarction and Intravascular hemolysis. Only a few important intramuscular hemolytic causes are mentioned here.

..Hemolytic anemia is classified as I. Inherited and II. Acquired.

 I. Inherited intravascular hemolysis due to 1. abnormal cell shape and size e.g. Thalassemia, Sickle cell anemia, Hereditary spherocytosis. Elliptocytosis.        2. Enzyme deficiency. G6PD (glucose 6 phosphatase deficiency) PKD (pyruvate kinase deficiency).

II Acquired hemolytic anemia. Burns. Autoantibodies –1. Immune hemolytic e.g., CLL (chronic lymphatic leukemia) Non-Hodgkin lymphoma. 2. Autoimmune hemolytic e.g., minor blood group Lupus erythematosus. 3. Autoimmune hemolytic e.g., post transfusion hemolysis, Hydrops fetalis and hemolytic anemia in newborn – Rh negative mother sensitized by Rh positive baby during pregnancy, mother's antibodies cross the placenta and hemolyze fetal RBCs of the subsequent pregnancy. 4. Drug induced antibodies e.g., Penicillin, Cephalosporins, Levofloxacin, NSADS, Methyldopa, Nitrofurantoin. 5. Mechanical causes- e.g. RBC breaks down in the microcirculation e.g., TTP (thrombotic thrombocytopenic purpura). ITTP (idiopathic thrombocytopenic purpura. Mechanical cardiac valves. 6. Miscellaneous e.g., PNH (paroxysmal nocturnal hemoglobinuria.

Hemolysis is due to the presence of antibodies. e.g., Cold agglutinins in mycoplasma pneumonia.

.. Bacterial hemolysins – cholera toxin, Clostridium perfriengence (gas gangrene, CMV, Rickettsia, Brucella, Trypanosoma, EBV (Epstein Barr virus).

 Autoimmune hemolytic anemia. Paroxysmal nocturnal hemolysis. Mediterranean fever.

..Other causes – Acute renal tubular necrosis. Acute glomerulonephritis, Good Pasture syndrome, snake bite, CO poisoning, barbiturate poisoning, polymyositis. muscular dystrophy, McArdle syndrome.

 ..Intracellular Parasites- Malaria, Babesia, Trypanosoma.

.. Black urine: Malignant melanoma.

..White urine. Lymphatic obstruction. Fungal UTI. Cellular derbies from TB.

. Snowflake urine. Calcium phosphate crystals.

. White cloud in oxalosis.

. Standing urine open to air changing to dark or black due to Alkaptonuria.

.. Spurious color changes – red diaper syndrome due to growth of bacteria Serratia marcescens.

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Sarcoidosis.

 

Sarcoidosis

PKGhatak, MD

In the old days of pulmonary tuberculosis, sarcoidosis was an interesting entity and entered into the differential diagnosis of pulmonary tuberculosis. Nowadays, sarcoidosis had taken that spot in the differential diagnosis of granulomatous diseases. This distinct applied to sarcoidosis because the cause of sarcoidosis is unknown, it can and usually affect multiple organs. Sarcoidosis may be self-limited or progressive or chronic. Sarcoidosis passes through three stages – inflammation, granuloma formation, fibrosis. Many other diseases have similar pathological characteristics. In short, sarcoidosis is diagnosed when all known causes of a granulomatous disease are eliminated.

Granuloma is a tiny localized collection of densely packed immune cells mostly macrophages, and epithelioid cells (elongated nucleus of macrophages), and a few Langhans giant cells (fusion of macrophages) surrounded by a zone of lymphocytes, eosinophils with some fibrosis at the periphery. The distinctive features of sarcoid granuloma are asteroid body- eosinophilic star shaped structures, and rounded laminated partially calcified structures called Schaumann bodies. The foreign-body granuloma at the center of the granuloma contains a part of the foreign body. Sarcoid granuloma is described as Non-Caseating granuloma. In the case of tuberculosis, the bacterial toxin causes the death of cells and matted dead cells are called caseation.

Sarcoidosis is due to the response of the Immunocytes to foreign agents/antigens. But the identity of the antigen and mechanism of the derailed function of Immune cells are not known. The hallmark of sarcoid is a granuloma. Immune cells fail to destroy the foreign antigen but contain it locally by forming a dense cellular wall around it.

 Common granulomatous diseases:

Foreign body – wood splinters, metal fragments, insect stings, spider bites. The ingrown root of the hair, tattoo ink, inhaled beryllium, dermal fillers collagen, forgotten sutures, aspiration of food particles in the lung.

Granulomatous polyangiitis or Wagner granulomas. - granuloma forms in the nasal passage, trachea, major bronchi. Hemoptysis is the presenting symptom.

Eosinophilic polyangiitis also called Churg-Struss syndrome, Necrotizing vasculitis of small and medium size vessels with peripheral eosinophilia and ANCA positive vasculitis. Patients present with asthma, weight loss and polyneuritis, bronchitis and other systemic symptoms.

Crohn's disease –  A chronic granulomas ulcerative lesion of the colon and terminal ilium and anal canal.

Rheumatic fever. Streptococcal antigen triggers granulomas on heart valves.

Rheumatoid arthritis. It is a debilitating chronic arthritis of the small joints of fingers, cervical spine, and knees; occasional granulomas in pleura and pulmonary fibrosis.

Mycobacteria infection. - Pulmonary tuberculosis, non-MT granulomatous diseases, Leprosy.

Bacterial. - Cat- scratch fever, Listeriosis,

Fungus. - Histoplasma, coccidoiodocomyces, blastomycosis, Cryptococcus.

Parasites. -Leishmaniosis of skin, liver and spleen; pneumocystis.

Symptoms of sarcoidosis are variable based on organ involvement:

Pulmonary lesions are 1. Hilar adenopathy in young adults must be differentiated from sarcoma by CT scan of the chest and abdomen and mediastinoscopy biopsy.2. Pulmonary infiltrates with or without adenopathy resembling pulmonary tuberculosis. Interferon gamma release assay, sputum smear and cultures for AFB and rarely bronchoscopic biopsy may be required. 3. Cavitary pulmonary lesion presented with hemoptysis. 4. Extensive pulmonary fibrosis and loss of lung tissue.

Skin: Lesions are. 1. Lupus pernio. - Disfiguring lesions of nose, cheeks, lips.2. Granuloma annuaries - flesh colored raised skin lesions on bony prominences and characterized by multiple rings. 3. Polyarteritis nodosa. - Raised painful nodules purplish blue color, appear in crops on the lower legs over the shin bones.

Heart. Heart block and other conduction abnormalities. Diagnosis is difficult if only a heart block is present. Liver biopsy is often diagnostic.

Eye. - Uveitis, chorioretinitis, sclerites, blindness. Dry eyes. Lachrymal gland biopsy may be required.

CNS. Facial nerve palsy is also called Bell's palsy, various neurological symptoms based on stages of the disease of CNS. Meningitis, seizures, dementia, polyneuropathy.

Kidneys. Recurrent renal stones.

Bones. Osteoporosis.

Blood. High calcium and markedly raised ACE (angiotensin converting enzyme), high ACE is also present in other granulomas but usually in the modest range. ACE is produced by granuloma cells.

Common symptoms at the time of presentation. The symptoms vary according to the organ involved. In the young adult male, hilar lymphadenopathy is usual. In general, the condition resolves spontaneously in 6 weeks. Recurrent skin lesions are common in blacks. Various eye lesions maybe not be so obvious initially but in chronic lesions, the eye involvement is usual. Dry eyes may require a biopsy of lachrymal glands for a diagnosis. Cavitary and progressive pulmonary fibrosis have a poor prognosis.

Treatment:

Treatment is urgent when eyes, heart CNS sarcoid lesions are present. Hypercalcemic may require emergency medical therapy.

Prednisone is the primary drug. Because of major side effects Methotrexate, Leflunomide, Hydroxychloroquine, Imuran, and cytotoxic drugs are added while the dose of prednisone is decreased or stopped.

Prognosis: Asymptomatic hilar lymphadenopathy has the best prognosis. Processive fibrosis has the worst outcome.

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