13 April 2016
Symptoms and signs of hypothyroidism vary according the severity of thyroid hormone deficiency. Nonthyroidal illnesses which coexist with hypothyroidism may alter the typical manisfestations of hypothyroidism.
In general, thyroid hormone deficiency causes a reduction in metabolic processes and matrix glycosaminoglycans accumulation in the interstitial spaces of tissue [Surks, 2016]. Other metabolic derangements include hyperlipidemia, hyponatremia, and impaired drug clearance. Hyperlipidemia occurs due to decreased lipid clearance, causing an elevation of serum free fatty acids and total and LDL cholesterol [Surks, 2016]. Hyponatremia occurs in about 10% of cases of hypothyroidism. It is seen only in severe myxedema. The cause is likely to be impaired cardiac function causing baroreceptor-mediated vasopressin secretion and total body water retention [Abuzaid and Birch, 2015].
Drug clearance is also reduced in hypothyroid patients. For instance, drug dosage must be lowered in antiepileptic, anticoagulant and opiod drugs to prevent drug toxicity [Surks, 2016].
There are marked cardiovascular derangements [Surks, 2016]. The thyroid hormone regulates genes that encode for enzymes responsible for myocardial contractility and relaxation. This, with the systemic hypometabolism, reduces heart rate and contractility which in turn lowers cardiac output. Reduced cardiac output contributes to exercise intolerance and exertional dyspnea experienced by hypothyroid patients. Patients may develop a pericardial effusion. The mechanism is probably increased systemic capillary permeability coupled with electrolyte disturbances. Tamponade may rarely occur [Patil et al, 2011].
There is a strong association with hypercholesterolemia, and a weaker but significant association with hyperhomocysteinemia [Morris et al, 2001]. Both increase the risk of cerebrovascular accidents [Morris et al, 2001; Mandava, 2015].
Although the low cardiac output can lead to hypotension, this typically occurs in cases of very severe hypothyroidism, such as myxedema coma [Wall, 2000]. More commonly, compensated hypothyroidism leads to a secondary hypertension [Stabouli et al, 2010].
The major gastrointestinal derangement is constipation. Ironically, the slow digestive transit often leads to “small intestinal bacterial overgrowth” (SIBO). SIBO is probably present in over half of all patients with hypothyoidism [Patil, 2014], and in occasional patients it may cause a chronic diarrhea.
Anemia is common. There are several causes. One cause is folate deficiency secondary to bacterial overgrowth [Surks, 2016]. This is typically normocytic, and normoblastic. Pernicious anaemia (in 10% of patients) may occur secondary to gastric atrophy that is sometimes associated with antiparietal cell antibodies (chronic autoimmune thyroiditis, eg. Hashimoto Thyroiditis). Pernicious anemia is macrocytic [Surks, 2016]. Iron deficiency anaemia may occur secondary to menorrhagia [Talley and O’Connor, 2014] – this is typically microcytic.
- General [Talley and O’Connor, 2014; Surks 2014]. The most important symptoms of hypothyroidism are
- cold intolerance
- weight gain
- lack of appetite
The important feature is weight gain despite a decreased appetite. It is typically modest, and results from reduced metabolic rate as well as fluid retention. Morbid obesity does not occur [Surks, 2016]. Fatigability is a very common, but nonspecific feature. In contrast, the cold intolerance, weight gain, and anorexia are very suggestive for hypothyroidism.
- Decreased sweating: this occurs from reduced calorigenesis and reduced acinar gland secretion [Surks, 2016].
- Brittle nails.
- Irregular menstruation in women
- Either oligo- or amenorrhea or hypermenorrhea-menorrhagia which causes decreased fertility and higher risk of early abortion[Surks, 2016]
- Hyperprolactinaemia may occur which leads to amenorrhea or galactorrhea[Surks, 2016]
- Decreased libido, erectile dysfunction and delayed ejaculation in men[Surks, 2016]
In general, hypothyroid patients present with slow mentation and speech, delayed relaxation of deep tendon reflexes, bradycardia, coarse hair and skin, puffy facies, tongue swelling and hoarseness of voice [Talley and O’Connor, 2014].
- Cool and pale skin with peripheral cyanosis due to decreased blood flow as a result of reduced cardiac output[Surks, 2016]
- Dry and rough as a result of atrophied epidermis and hyperkeratosis of skin[Surks, 2016]
- Skin discolouration: a yellowish tinge may occur from hypercarotenemia due to slowing down of hepatic metabolism of carotene[Talley and O’Connor, 2014]. Hyperpigmentation may occur when there is primary hypothyroidism associated with primary adrenal failure, there is high ACTH secretion causing increased level of melanocyte stimulating hormone (MSH) with deposition of pigments on skin[Surks, 2016].
- Coarse hair with loss of hair or thinning of the outer third of the eyebrow associated with myxedema [Surks, 2016]
- Myxedema (non-pitting edema)
- Vitiligo and alopecia areata (spots of baldness. These are autoimmune in origin, and occur in patients who have been treated for Graves’ disease and now present with hypothyroid [Surks, 2016].
- Periorbital edema due to generalized non-pitting edema (myxedema)
- Xanthelasma as a result of hypercholesterolemia as a result of decreased fat metabolism[Talley and O’Connor, 2014]
- Graves’ ophthalmopathy. After treatment of Graves’ hyperthyroidism, the patient might develop hypothyroidism but the features of Graves’ may persist. Presenting with stare, proptosis and weakness of extraocular muscle/ ophthalmoplegia[Surks, 2016]
- Abuzaid AS, Birch N. The Controversies of Hyponatraemia in Hypothyroidism. Sultan Qaboos Univ Med J. 2015 May; 15(2): e207–e212.
- Mandava P. Homocystinuria/Homocysteinemia. Medscape, updated 3 Nov 2015, accessed 13 Apr 2016, http://emedicine.medscape.com/article/1952251-overview#a1.
- Morris MS, Bostom AG, Jacques PF, Selhub J, Rosenberg IH. Hyperhomocysteinemia and hypercholesterolemia associated with hypothyroidism in the third US National Health and Nutrition Examination Survey. Atherosclerosis. 2001 Mar;155(1):195-200.
- Patil, AD. Link between hypothyroidism and small intestinal bacterial overgrowth. Indian J Endocrinol Metab 2014;18(3):307-9.
- Patil VC, Patil HV, Agrawal V, Patil S. Cardiac tamponade in a patient with primary hypothyroidism. Indian J Endocrinol Metab. 2011 Jul; 15(Suppl2): S144–S146.
- Stabouli S, Papakatsika S, Kotsis V. Hypothyroidism and hypertension. Medccape, accessed 13 Apr 2016, http://www.medscape.com/viewarticle/733788.
- Surks M, ‘Clinical manifestations of hypothyroidism’, UpToDate, http://www.uptodate.com.ezproxy.lib.monash.edu.au/contents/clinical-manifestations-of-hypothyroidism?source=machineLearning&search=clinical+features+of+hypothyroidism&selectedTitle=1~150§ionRank=1&anchor=H2#H2 , last updated on Mar 08, 2016, accessed on Apr 02, 2016.
- Talley NJ & O’Connor S, ‘The Endocrine Examination’, Hunter C, Clinical Examination: A systematic guide to physical examination, 7th edn, Elsevier Australia, Chatswood, 2014; pp 360-362.
- Wall CR. Myxedema coma: diagnosis and treatment. Am Fam Physician 2000 Dec 1;62(11):2485-2490.