Are You Confident of the Diagnosis?
Myxedema is characterized by swollen, dry, pale, and waxy induration of the skin caused from depositions of mucopolysaccharides in the setting of hypothyroidism versus hyperthyroidism, which can manifest with pretibial myxedema. Generalized myxedema is the most characteristic cutaneous finding of hypothyroidism. This deposition is not specific to the dermis and may deposit in any organ, and thus systemic manifestations may occur.
Characteristic findings on physical examination
Skin manifestations: swollen, dry, pale, with a waxy and firm appearance. It may have the appearance of edema as you would see in venous stasis disease, but will not pit upon pressure. The appearance may be sallow because of a carotenemia. Facial manifestations may include ptosis, swollen lips, macroglossia, a broad nose along with puffy and drooping eyelids.
Other cutaneous signs of hypothyroidism include dry skin, thin hair and nails. Dry skin and pruritus is one of the most common symptoms seen of hypothyroidism but not specific. The mechanism, however, is unknown. Palmoplantar keratoderma can also be seen. A recent report highlights a decrease in wound healing in mice which emphasizes the overall important activity of thyroid hormones in the skin.
Hair manifestations are dry, coarse, brittle hair with a decreased diameter. The appearance may be thinner due to increased breakage, decreased diameter or thickness of each hair and increased loss of number of hairs. Madarosis (hair loss on outer 1/3 of eyebrows) may also be seen in hypothyroidism. Nails are typically thin, dry, and brittle. There may be an increased risk for purpura due to increased mucin and decreased clotting factors.
Expected results of diagnostic tests
Diagnosis can be confirmed with serum levels of TSH and antithyroid peroxidase antibodies and/or antithyroglobulin antibodies, which can confirm hypothyroidism and Hashimoto’s thyroiditis. TSH will be high unless the hypothyroidism is central hypothyroidism; in these cases free T4, total T3, and total T4 may be needed for diagnosis.
Though uncommon in the United States and other first world countries due to neonatal screening, cretinism is the condition of stunted physical and mental development due to the lack of treatment of congenital hypothyroidism. The most common etiology is due to maternal hypothyroidism.
Who is at Risk for Developing this Disease?
The National Health and Nutrition Examination Survey (NHANES) III study notes that 4.6% of the population may suffer from hypothyroidism (0.3% clinical and 4.3% subclinical). In the United States, the most common cause is from Hashimoto's thyroiditis. There are three different settings of hypothyroidism: congenital, juvenile, and adult.
Adult hypothyroidism: risks include over 50 years old; female. Certain drugs or iatrogenic causes exist and can cause hypothyroidism (amiodarone, lithium, bexarotene, potassium iodide, radiation to the brain, or propylthiouracil, which is used to treat hyperthyroidism). Pregnancy can cause a transient hypothyroid state or herald the onset of Hashimoto's thyroiditis.
What is the Cause of the Disease?
Myxedema is secondary to hypothyroidism, which is decreased amount or function of thyroxine.
Reports conflict on whether there is increased deposition of mucopolysaccharides or decreased degradation of mucin. There are typically normal or inactive dermal fibroblasts, which shows that the thickening of the skin from increased amount of mucin regardless of the mechanism. Typically there is no new collagen deposition.
Systemic Implications and Complications
Other aspects that can be seen with hypothyroidism include the risk for purpura, cold, pale, skin. Carpal tunnel or facial nerve palsy has been seen with the mechanism thought to be from deposition of mucin peripheral to the affected nerve, though not proven.
Ophthalmopathy is rare with Hashimoto's thyroiditis but would manifest with diplopia, conjunctival injection, lagophthalmos and decreased vision. However, the pathogenesis has not been elucidated.
Nail changes have an increased incidence of Candida albicans infections.
Weight gain, constipation, cold intolerance, galactorrhea.
Lack of treatment and prolonged hypothyroidism may result in myxedema coma, which can result in death. This can be preceded by psychosis, irritability, bradycardia, shortness of breath, loss of memory, and severe depression. Carotenemia has also been reported in the later stages of untreated hypothyroidism.
Medicine: L-thyroxine replacement. With infantile hemangiomas, the treatment with oral propranolol has decreased the hemangiomas and resolved the hypothyroidism.
Skin: lubrication and hydration
Optimal Therapeutic Approach for this Disease
All patients with suspected hypothyroidism should have a screening TSH and if abnormal referred to an endocrinologist or internist. Patients with suspected hypothyroidism with a normal TSH should be referred to endocrinology for a complete hormonal workup.
All treatment options revolve around increasing the amount of thyroid hormone. L-thyroxine replacement at starting dose of 1.6mcg/kg of weight is recommended and followed to normalize TSH levels (checked every 4 to 6 weeks) and symptom control. Caution in patients with cardiac comorbidity in particular should be considered to prevent side effects and secondary cardiac events from those side effects. Usually, this medicine is to be taken for the rest of one's life.
Hair: Thyroid replacement has been shown to normalize the telogen/anagen ratio.
Skin: Therapy is optimization of hydration of the skin. This would include alpha-hydroxy acids such as 12% ammonium lactate, ointments (Vaseline or Aquaphor), oils, urea or any lubricating cream (Cetaphil or Cerave for instance).
Once the patient is on a stable dose of thyroid hormone, checking the levels yearly would be indicated.
High fiber diets and soy products can alter absorption. If dietary modification occurs one may want to check thyroid levels more regularly than every year. Patients should also consider not taking their thyroid hormone replacement with any multivitamin, aluminum hydroxide antacids or medicines that bind bile acids as it alters absorption of the hormone.
Unusual Clinical Scenarios to Consider in Patient Management
There are many different conditions that have been reported to be associated with thyroid disease. These include alopecia areata, anemias, bullous disorders (pemphigus and pemphigoid), connective tissue diseases (lupus and dermatomyositis), other endocrinopathies, vitiligo, urticaria and Sweet's syndrome. Appropriate history and physical should be accomplished to rule out associated conditions. Recent articles demonstrate hypothyroidism (70% incidence in one series) with infantile hemangioma patients, which is likely due to increased utilization of the hormone by the hemangioma.
Congenital hypothyroidism occurs in 1 to 4000/5000 births with females 2:1 over males. An analysis of the thyroid gland should be done as this is the primary cause. If this is missed, the subsequent abnormalities include dwarfism, mental retardation, and a myriad of cutaneous changes. This can worsen to include poor feeding, bradycardia, hypothermia and enlarged posterior fontanel. Routine newborn screenings are mandatory within the United States, which is important as 33% may present with no abnormal signs or symptoms. A clavicular fat pad is very characteristic according to some sources.
It has been increasingly recognized that infantile hemangiomas may also lead to consumptive hypothyroidism with the same issues noted above and should be screened for in infants with any large or multiple hemangiomas. Ultrasound evaluation in particular is helpful in delineating how large the hemangiomas may be and to monitor treatments. This consumptive hypothyroidism is likely due to overexpression of type 3 deiodinase in the endothelium of vascular tumor. Oral propranolol has shown improvement in hemangioma size and resolution of the hypothyroidism.
What is the Evidence?
Kopp, SA, Ferzli, PG, Hivnor, CM, Heymann, WR., Heymann, WR. "Cutaneous manifestations of hypothyroidism". Thyroid disorders with cutaneous manifesations. Springer. 2011. pp. 89-102.(Text with 14 chapters of every aspect of thyroid disease and the associated cutaneous manifesations. This chapter specifically deals with hypothyroidism and its cutaneous manifestations.)
Saadia, Z, Alzolibani, AA, Al Robaee, A, Al Shobaili, HA, Settin, AA.. "Cutaneous manfestations of hypothyroidism amongst gynecological consultations". Int J Health Sci. vol. 4. 2010. pp. 168-77.(Case control study looking at consultation comparing hypothyroid and euthyroid. Cutaneous differences included increased risk for urticaria and puffiness of the hands and feet, yellow to ivory skin in patients with typically dark type 4 to 5 skin, and rough dry skin. Only hypothyroid patients had alopecia and periorbital edema. Gynecologic differences were discussed as well.)
Cho, SB, Kim, JH, Cho, S, Park, JM, Park, YK, Oh, SH.. "Vitiligo in children and adolescents: association with thyroid dysfunction". J Eur Acad Dermatol Venereol. vol. 25. 2011. pp. 64-7.(Analysis of vitiligo patients and thyroid dysfunction; 15 of 254 patients (5.9%) had thyroid disease. Interestingly, 0 of 50 patients with segmental vitiligo had any thyroid dysfunction.)
De Corti, F, Crivellaro, C, Zanon, GF, Luzzatto, C.. "Consumptive hypothyroidism associated with parotid infantile hemangioma". J Pediatr Endocrinol Metab.. vol. 28. 2015. pp. 467-9.(Describes one case among many of consumptive hypothyroidism in infants with infantile hemangiomas.)
Contreras-Jurado, C1, García-Serrano, L1, Martínez-Fernández, M. "Impaired hair growth and wound healing in mice lacking thyroid hormone receptors". PLoS One. vol. 9. 2014. pp. e108137.(Report that discusses in detail thyroid receptors and hormones and their expression in follicular and skin cells.)
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