Thyroid and Adrenal Disorders

Thyroid and Adrenal Disorders

1. PRIMARY thyroid disorders - problems with the thyroid itself that lead to increased or decreased secretion of thyroid hormones.

2. SECONDARY thyroid disorders - Problems with the hypothalamus/ pituitary axis - leading to problems with over/under production of thyroid hormones. As the hypothalamus and pituitary control endocrine functions in many organs these patients are likely to have problems at other targets.

3. HYPOthyroidism - 'suppressed metabolism' - symptoms include: extreme fatigue, hair loss, lethargy, muscle aches and weakness, constipation, intolerance to the cold, weight gain, facial and eyelid oedema.

   • 'Hashimoto's' - the most common primary hypothyroidism condition due to autoimmune destruction of the thyroid gland - symptoms result from a lack of the thyroid hormones T3 and T4 (T4 is converted to T3 in the body), these hormones are lacking although TSH (thyroid stimulating hormone) from the pituitary gland is increased in an attempt to stimulate the thyroid to produce more T3, T4.
   • Treatment: Replacement of the thyroid hormones. T4 - Levothyroxine (most commonly used) or T3 - Liothyronine (used if the patient has problems converting T4-T3).
     • Levothyroxine (thyroxine) in patients <60 years in the absence of ischaemic hear disease: 50-100mcg daily increasing the dose up to a maximum of 100-200mcg daily (at intervals of 4 weeks, increased by 25 to 50mcg to max) Patient dose determined by the target TSH concentrations of 0.5-2mU/L.
       • TSH release is regulated by TRH (thyrotropin releasing hormone) from the hypothalamus and negative feedback from the thyroid hormones, predominantly T3, on the pituitary. Patients with Hypothyroidism will have elevated levels of TSH (>5mU/L) - in an attempt to stimulate the thyroid to release more T4/T3.
         • T4 is converted into the more potent T3.
       • In patients >60 years or in those with ischaemic heart disease a lower dose is started: 25-50mcg daily, increasing by 25mcg according to response at intervals of 4 weeks to a maximum dose of 100-150mcg. Patients in this group have a more lenient TSH target of 0.5-5mU/L as there are increased risks of over-replacement in this population (arrhythmias, increased systolic blood pressure).
     • Levothyroxine must be taken on an empty stomach (1/2 hour before food or 2 hours after food) and cannot be taken with dairy, antacids, mineral supplements due to decreased absorption. Eutroxsig and Oroxine must be refrigerated.
   • Thyroid cells are destroyed by the immune system; antibodies and Cytotoxic T-cells.

4. HYPERthyroid - 'overactive metabolism' - symptoms include: enlarged thyroid (goitre), tachycardia, increases in systolic BP, weight loss, muscle wasting, tremor, intolerance to heat.

   • 'Graves disease' is the most common from of hyperthyroidism. These patients have an increased metabolism due to excess thyroid hormones which can result in increased drug metabolism (increased clearance) - which may require larger doses of other medications and dose reductions as they become euthyroid (normal thyroid function), they can also have increased sensitivity to anticoagulants due to increased breakdown/catabolism of vitamin K dependant clotting factors.
     • Hypothyroidism in pregnancy - occurs in 1-2 mothers in very 1000, both PTU and Carbimazole are category C in pregnancy - "due to pharmacological effect have cause, or may be suspected of causing harmful effects on the foetus without causing malformations" - PTU is used in the 1st trimester and Carbimazole is used in the 2nd and 3rd trimester.
   • Treatment: Antithyroid drugs, destruction of thyroid cells with radioactive iodine, total thyroidectomy (removal of the thyroid). Over-treatment will result in Hypothyroidism and require replacement with Levothyroxine.
     • Block and replace treatment: A large dose of an anti-thyroid drug (Carbimazole or PTU) to completely suppress thyroid function and then give thyroxine to replace as needed.
   • Severe hyperthyroid (thyroid storm): initial treatment with high dose ant-thyroid drug. And ongoing treatment with Carbimazole or Propylthiouracil with dose tailored to achieve normal T4 and T3 levels - TSH may take longer to normalise.
     • Beta blockers may be used to control the symptoms of tachycardia, tremor and sweating. Non-selective beta blockers (Propranolol) help these sympathetic responses as a 'bridging' therapy - between treatment starting and the relief of symptoms (thyroxine has a long half life - the production may be stopped initially but hormones in circulation can still have their effect.
       • In many tissues hyperthyroidism is associated with an increased number of beta-adrenergic receptors - the increase in beta activity is associated with many of the symptoms of hyperthyroidism and explains why beta-blockers are so effective in relieving these symptoms in patients.
         • Propranolol is also thought to block the enzyme that is involved in the conversion of T4 to the more potent T3, resulting in the production of an inactive T3.
           • If beta-blockers are contraindicated (asthma) then Diltiazem (rate-limiting/non-dihydropyridine calcium channel blocker) may be used - wont be effective at blocking the sympathetic symptoms of hyperthyroidism like beta-blockers are.
     • Carbimazole (anti-thyroid drug): Blocks thyroid hormone synthesis. 20mg oral, 8 hourly.
       • Adverse effects from anti-thyroid drugs: Itching and mild skin rashes (most common during first 8 weeks, might respond to an antihistamine, switching to alternative antithyroid drug may help - although 30-50% of patients cross react), arthralgia (joint pain), hepatotoxicity, agranulocytosis.
         • Agranulocytosis: presents as high fever, severe pharyngitis (sore throat), mouth ulcers, acute malease (general body weakness). Agranulocytosis is a reduced/non-existent population of neutrophils (WBC) making the patient very susceptible to infection. Occurs very suddenly - routine blood testing unlikely to make any difference - health professionals and patients need to be aware of the signs.
     • Propylthiouracil (PTU) (anti-thyroid drug): Blocks thyroid hormone synthesis and inhibits the peripheral conversion of T4 to T3. 200mg oral 4-6 hourly.
     • Lugol's (iodine) solution: inhibits thyroid hormone release, given 1 hour after PTU.
     • Dexamethasone: corticosteroids inhibit the peripheral conversion of T3 to T4.
   • TSH receptor antibody binds to TSH receptor on thyroid cells and triggers thyroid hormone production and thyroid enlargement (hyperplasia).

5. Addison's Disease: Presentation - bronze pigmentation of the skin, postural hypotension, weight loss - can lead onto adrenal crisis: profound fatigue, dehydration, collapse of the vasculature (decreased blood pressure), renal shut down. Adrenal crisis can be triggered from stresses such as injury, illness, surgery or infection.

   • Addison's disease is known as primary adrenal insufficiency or hypocortisolism - the adrenal glands (above the kidneys) do not produce enough of the steroid hormone cortisol - likely due to damage by the body's own immune system or the long term use of corticosteroids.
   • Management: Replacement of the missing cortisol in a regime as close to the normal physiological cortisol fluctuations.
     • Cortisol is a steroid hormone (in the glucocorticoid class), produced naturally in the adrenal cortex (within the adrenal gland) and is released in response to stress and low blood glucose concentrations - with the function to increase blood sugar (through gluconeogenesis - generation of glucose from the breakdown of protein and other non-carb sources), also functions to suppress the immune system and decrease bone formation.
     • Hydrocortisone 0.24mg/kg PO D in 2-3 divided doses.
     • Cortisone Acetate 0.3mg/kg PO D in 2-3 divided doses.
     • Prednisolone 5mg PO Mane.
     • Primary adrenal insufficiency needs glucocorticoid and mineralocorticoid replacement. These are both produced by the adrenal cortex and require replacement.
       • Glucocorticoids - cortisol - immune regulation and glucose metabolism.
       • Mineralocorticoids - aldosterone - sodium and water balance in the kidneys.
       • The drugs used for Addison's disease have potency at both glucocorticoid and mineralocorticoid receptors - although each differs in relative potency.
     • Dosing: 40-60% of daily dose as soon as they wake up, 25-35% midday and 15-25% late afternoon (before 5pm) - to replicate the normal physiological release of cortisone. In periods of stress (acute illness, stress) higher dosing is required as this is how the body responds to these situations - by increasing cortisol release.

6. Cushing's syndrome: presentation - moon face, fat deposits on the face and back of the shoulders, thin skin, osteoporosis, thin arms and legs in proportion to enlarged torso, hyperglycaemia.

   • Cushing's syndrome can be caused by excess cortisol (from oral corticosteroids), doses or more than 7.5mg a day of Prednisolone are supraphysiologic (more than normally found in the body). Can also be caused by a tumor in the pituitary - leading to excess secretion of cortisol from the adrenals.
     • There is limited use of drug therapy in this syndrome/disease - it is mostly managed by surgery. Pharmacological blockage of adrenal corticosteroid production may be required before surgery, if surgery has been unsuccessful and if the source of the excess ACTH is unclear.
       • Ketoconazole - 200mg PO BD, increasing dose every 3 days.
       • Metyrapone -
       • Mitotane -

Images and files in the map