Parathyroid gland – sees the free calcium in the blood

You have probably never heard of any disorders related to this gland, but they do occur.  The parathyroid gland has chief cells that regulate the free calcium ion via the secretion of PTH.

When blood has low calcium, PTH is released from chief cells of the parathyroid gland and has 3 functions:

1. PTH activates osteoblast =>stimulate osteoclast => resorb bone to release calcium AND phosphate in blood

2. In the small bowel, it activates vitamin D => which helps absorb calcium AND phosphate.

3. In the kidney, it stimulates Gs receptors in distal tubule to reabsorb calcium and decreases phosphate reabsorption in proximal tubule.

When there is enough serum ionized calcium level then the PTH secretion decreases via negative feedback.


Primary: parathyroid adenoma (80%), sporadic parathyroid hyperplasia, parathyroid carcinoma.

Secondary: disease outside the parathyroid gland causing the parathyroid gland to increase PTH secretion



Thyroid problems – many women suffer from these

You could have hyper or hypothyroidism.

The basic principles behind hyperthyroidism is that there is an increased level of circulating thyroid hormone. This results in an increased basal metabolic rate (d/t inc synthesis of Na/K ATPase) and increased sympathetic nervous system activity d/t inc expression of B1 adrenergic receptors. From this, the clinical features of hyperthyroidism arise, which are HYPOcholesterolemia, oligomenorrhea, staring gaze w/ lid lag, heat intolerance, sweating, and increased everything else.

There are two disease that can cause hyperthyroidism: Grave’s disease and multinodular goiter.

1. Grave’s dz: This is the MCC of hyperthyroidism and occurs in childbearing aged women (20-40y/o) Autoantibody (IgG) stimulates TSH receptor via a Type II hypersensitivity rxn=> inc synthesis and release of thyroid hormone. They get

On H&E, we would see irregular follicles w/ scalloped colloid and chronic inflammation.

On labs we would see a decrease in TSH because the elevated free T4 down regulates TRH receptors in the anterior pituitary to decrease further TSH release. There is also an increase in total T. We would also see HYPOCHOLESTEROLEMIA and INCREASED SERUM GLUCOSE.

Treatment involves: B-blockers, thioamide ( blocks peroxidase), and radio iodine ablation (radioactive iodine taken up by cell).

The feared, fatal complication is a thyroid storm! increased catecholamines and hormones, usually in response to stress (surgery, childbirth( => arrhythmia, hyperthermia, vomiting w/ hypovolemic shock.
We give Propylthiouracil (PTU, which inhibits peroxidase AND peripheral T4=>T3 conversion), B blockers, and steroids.

The second pathology that can cause too much thyroid hormone (hyperthyroidism) is a multi nodular goiter. A multinodular goiter causes the the thyroid gland to enlarge because there is a relative iodine deficiency. This is non toxic (euthyroid) usually and rarely some parts of the gland become TSH independent and start releasing more T4 – hyperthyroidism (toxic goiter).


1. Cretinism – neonates and infants; needed thyroid hormone for normal brain and skeletal development.

short, enlarged tongue, umbilical hernia, coarse facial features, MR

2. Myxedema – children and adults. MCC if iodine deficiency.

dough like consistence d/t GAG deposits in skin and soft tissue => deepening of voice and large tongue.  Oligomenorrhea, hypercholesterolemia.


1. Hashimoto Thyroidits- MCC of hypothyroidism if iodine levels are normal. HLADR5 ass’d autoimmune dz.  This starts as hyperthyroidism because the follicles are destroyed then becomes hypothyroidism. You can also see if damage to the thyroid gland was done by looking for antithyroglobulin and antimicrosomal antibodies. Unfortunately, if the thyroid gland is enlarging there is an increased risk for B cell (marginal zone) lymphoma.

2. Subacute granulomatous De Quervain Thyroiditis post viral infection. TENDER thyroid gland w/ TRANSIENT HYPERTHYROIDISM Self -limited so never becomes hypothyroidism.

3. Reidel Fibrosing Thyroiditis – chronic inflammation w/ fibrosis of thyroid gland results in hard as wood non-tender gland. Fibrosis may extend into local structures (airway), thus you may think it is anaplastic carcinoma, but Reidel Fibrosing Thyroiditis patients are younger (40s) and malignant cells are not there.

Diabetes means to urinate too much

Are you not peeing much? You may have…Syndrome of Inapproate ADH (SIADH) secretion.

Like the name suggests, your body makes too much ADH usually due to and ectopic production (e.g. small cell carcinoma of the lung); or CNS trauma, pulmonary infection, and drugs (e.g. cyclophosphamide).

Because you are retaining lots of free water, sx include: body electrolytes being diluted by the large amount of retained water (hyponatremia and low serum osmolality) and the hyponatremia leads to neuronal swelling and edema (mental status changes and seizures)

Tx = restrict free water (because your body has enough of that) and demeclocycline (which is a tetracycline that somehow competes with ADH)

Diabetes means to urinate too much. There are many causes of urinating too much. Three things that can cause polyuria are DM, Diabetes insipid us, or psychogenic insipid us. It could be Type I Diabetes, Type II Diabetes Mellitus, Central Diabetes Insipidus, or Nephrogenic Diabetes insipidus. On the other hand, you may not urinate a lot if you have Syndrome of inappropriate ADH (SIADH) secretion.

Antidiuretic hormone (ADH) prevents you from urinating. ADH along with oxytocin is made in hypothalamus (supraoptic nuclei) then transported via axons to the POSTERIOR pituitary for release. ADH works on distal tubules and collecting ducts of kidneys to promote free water retention. The primary fxn of ADH is serum osmolarity regulation (ADH ==> dec serum osmolarity and inc urine osmolarity) via regulation of aquaporin channel transcription in principal cells of renal collecting duct. It is regulated by osmoreceptors in the hypothalamus (primary) and hypovolemia (secondary). Oxytocin mediates uterine contraction during labor and causes let-down (release of breast milk) in lactating mothers.

  1. Central Diabetes Insipidus – can’t make ADH
    1. Dx: water deprivation test doesn’t increase urine osmolality
    2. tx: desmopressin, an ADH analog
  2. Nephrogenic Diabetes Insipidus – Kidneys can’t respond to ADH
    1. inherited mutations or drugs (lithium and demeclocycline)
    2. tx: can’t use ADH analog, since ADH is not the problem here

Clinical features of both of these posterior pituitary diabetes are based on loss of free water d/t lack of ADH effects. They include:

  1. pee it out therefore you are more thirsty (polyuria and polydipsia – risk of life-threatening dehydration)
  2. There is less water in your body to dilute your electrolytes (hypernatremia and high serum osmolality)
  3. And too much water in your urine so diluted urine electrolytes (low urine osmolality and specific gravity)

Two HYPERGLYCEMIC states leading to DIABETES either via NO insulin or INEFFECTIVE insulin

The two other ways by which you may be urinating too much are Type I and Type II Diabetes Mellitus. They are both based on the Endocrine Pancreas pathology. The normal endocrine pancreas is made of cluster of cells called the Islets of Langerhans. One islet is made of many different cell types, each producing one hormone. The beta cells, which lie in the center of the Islets make Insulin.

What is Insulin, you ask?

Insulin is an anabolic hormone (helps make bigger molecules from smaller molecules to store energy), which increases insulin-dependent transporter protein (GLUT 4) on skeletal muscle and adipose tissue, so that GLUT 4 can suck up the glucose from the blood into your skeletal and adipose cell. Once glucose is inside cell, it results in can be stored (glycogenesis), made into fat (lipogenesis), and protein (protein synthesis).

Insulin’s archnemesis is glucagon. It is made by alpha cells and increases blood glucose levels in fasting states when there is low glucose via glycogenolysis and lipolysis.

3. Type I Diabetes Mellitus

Autoimmune antibodies against Insulin ass’d w/ HLA-DR3 and HLA-DR4. No insulin, so glucagon wins and leads to gluconeogenesis, glycogenolysis, and lipolysis, which leads to even more hyperglycemia.

Tx= lifelong insulin

Diabetic Ketoacidosis is advanced Type I DM:

  • stress (viral infection)=>epinephrine => glucagon =>inc lipolysis =>inc free fatty acids =>liver converts them to ketone bodies (B-hydroxybutryic acid > acetoacetic acid)
  • hyperglycemia (>300 mg/dL), anion gap metabolic acidosis d/t hyperkalemia (hyperK arises bc insulin usually drives K inside cell and K is also released to combat the metabolic acidosis)
  • sx: Kussmaul respirations, fruity smelling breath d/t acetones, dehydration, N/V, mental status changes
  • Tx:
    • fluids (correct dehydration from peeing too much – polyuria)
    • insulin – drives the glucose and K back into cell, also counteracts glucagon
    • electrolytes – K

4. Type II Diabetes Mellitus

Type II Diabetes Mellitus is an increasingly common disease in United States. Adult-onset diabetes is tightly linked to genetics and obesity. As Americans become more obese, their cells decrease the number of insulin receptors leading to an increase in insulin resistance. Therefore, they need more insulin to drive the same amount of glucose in their cell. Eventually B-cells is exhausted and amylin can be seen deposited in the islets. Can no longer make endogenous insulin.

Schwann cells can take up glucose without insulin. Aldose reductase will convert glucose into sorbitol, sorbitol leads to osmotic damage and lysis. This leads to the neuropathy seen in Diabetes.  Underneath the endothelial cells, there are pericytes  which can take up the glucose and aldose reductase converts it into sorbitol and pericytes die. P the wall of blood vessel weakens and forms an aneurysm => blindness. The lens also can take up glucose where aldose reductase converts it to sorbitol and and leading to osmotic lysis.

Risk of hyperosmolar non-ketotic coma in uncontrolled type II DM

  • high glucose (>500 mg/dL) => life threatening diuresis w/ hypotension and coma
  • Ketones are absent because there is small amounts of insulin circulating,(so glucagon doesn’t cause lipolysis?)

Long term consequences of Type II DM

  1. Nonenzymatic glycosylation (NEG) of all vascular basement membrane
    1. NEG of large and medium sized vessels => ATHEROSCLEROSIS! (yikes!)
      1. cardiovascular dz =>MCC of death in diabetics
      2. peripheral vasc dz => MCC of nontraumatic amputations
    2. NEG of small vessels (arterioles) => HYALINE ARTERIOCLEROSIS (onion-like)
    3. NEG of Hemoglobin => glycated hemoglobin (HbA1c) – marker of glycemic control over the past 3 months
  2. Osmotic Damage
    1. non-insulin dependent cells take up excess glucose => Aldose reductase converts glucose to sorbitol => osmotic pull of water into cell
    2. non-insulin dependent cells = Schwann cells which myelinate peripheral nerves, retinal blood vessels, lens

Lacunar infarcts can occur in uncontrolled DM and HTN

How would you know if you have Diabetes?

Your doctor will do a blood test, in which she will look at the glucose concentration.

Normal glucose concentration is 100 mg/dl. If you did not fast, then it’s called a random glucose test, and >200mg/dL

fasting glucose test * preferred test fro type 2 and type1 = >126 mg/dl on 2 occassions

oral glucose tolerance test is mostly used in pregnancy . Your doctor will make you drink a sweetened glucose drink and test the glucose levels to see how much glucose was driven into cells after 2 hours. >200 mg/dl is again diagnostic for Diabetes.

I have diabetes” what can I do?”

The number 1 treatment is diet and exercise

metformin (a biguanide) is the number 1 medication given after diet and exercise.

TZD – thiazolidinediones – improve insulin resistance by binding to PPAR gamma, transcription regulator of genes involved in glucose and lipid metabolism. PPAR gamma codes for adiponectin, a cytokine secreted by fat tissue. adiponectin is low in type 2 DM, TZD increases these levels =>dec insulin resistance.

s.e fluid retention => wt gain and worsens CHF

sulfonylureas – bind to KATP => close channels =? depolarizes beta cell => volt gated ca channel opens => ca influx => exocytosis on insulin

insulin – binds to cell surface receptor. alpha subunit binds insulin. beta subunit has tyrosine kinase

enzyme inactivation metformin (hepatic microsomes) and alpha-gluosidase inhibitors (membrane-bound disaccharides on brush border)

glucagon like polypeptide 1 – incretin hormone secreted bt intestinal L cells in response to food intake. Keeps you full longer and decreases gastric emptying. It also increases  insulin release from beta cells. works through adenylate cyclase system.  but too short half life to be used clinically.

First entry/Boards prep

I chose the train as my blog theme because it will remind me of my desire to move to a big city. Big cities have so much entertainment and mental stimulation to offer that small towns just can not.

I just finished studying Genetics and did Genetics Qbank. Wow! I didn’t realize how much time was involved in doing these questions. Genetics is only a small portion of the Boards, yet it took forever. I am now going to review the wrong answers and move on to the next subject.