Abstract

Hyperpigmentation is a common dermatologic condition among patients of all skin types. Pigmentation disorders are the third most common among dermatologic disorders and cause significant psychosocial impairment. In this case we will discuss diffuse hyperpigmentation induced by Graves disease. The diffuse hyperpigmentation in Graves disease was caused by elevated adrenocorticotropic hormone (ACTH) as well as anti- TSH receptor stimulating antibody instead of enhanced capillary fragility. Other potential mechanisms for skin pigmentation in hyperthyroidism still need further exploration.

Introduction

Endocrine diseases usually cause a diffuse hyperpigmentation which may be generalized or limited to certain area, such as Addisons disease and hemochromatosis. Generalized diffuse hyperpigmentation of the skin is seen, which is classically described as “bronzing.” The hyperpigmentation is more prominent on the sun-exposed skin, pressure points (elbows and knees), and normally pigmented areas (creases, knuckles, perineum, axillae, areolae, palms, and soles). This hyperpigmentation is caused by the increased levels of beta-lipotropin or ACTH, each of which can stimulate melanocyte production

Hyperthyroidism mainly leads to dermal symptoms like localized myxoedema, eczematous dermatitis, alopecia, and telangiectasis. There had been a hypothesis that thyrotoxicosis could also lead to hyperpigmentation through an increased capillary fragility, contributing to hemosiderin deposition and basal melanosis.

In this case report, we try to elucidate the possible mechanism for hyperpigmentation in Graves disease.

Case report

A 42-year-old woman came with the complaint of pigmentation and weight loss for 3 months. She had diffused hyperpigmentation observed on the whole body including non-sun-exposed skin, especially on her lower and upper extremities, as well as her face.

Over the past 3 months, despite an increase in appetite, she had weight loss for 15 kg. She gave a recent history of menstrual irregularities, heat intolerance, fine tremor, palpitations, and anhelation after regular exercise at times. She has no sign of exophthalmos, conjunctival edema, and myxoedema. Her thyroid gland was diffusely enlarged (WHO goiter grading I) with elastic hardness.

On examination, the electrocardiogram revealed a heart rate with 95 beats/min at rest. Technetium-99 m-methoxyisobutylisonitrile (MIBI) scintigraphy demonstrated a diffusely increased uptake rate to 18.5% (positive >2.5%) in the thyroid gland, a pattern consistent with Graves disease. Thyroid ultrasonography scans showed mild goiter and Color flow Doppler imaging demonstrated high blood flow, while adrenal ultrasonography was normal. The histopathological examination from pigmented skin revealed hyperpigmented basal cells in the epidermis as well as lots of melanophages in the superficial dermis. Iron staining to identify the presence of hemosiderin deposition showed negative results.

The patient was diagnosed with hyperpigmentation induced by Graves disease, thus was treated with tretinoin 0.05%, and beta blocker for thyroid dysfunction. A month later, the hyperpigmentation abated and the thyroid function improved. Moreover, the adrenocortical functions returned to normal levels. Three months later, the thyroid function came to normal and skin pigmentation further subsided.

Discussion

In our case, we hypothesized that hyperpigmentation in skin may be correlated with the following explanations. First, increased release of pituitary ACTH in the thyrotoxicosis patients could compensate for accelerated cortisol degradation. Pituitary ACTH, in common with some MSH peptides in the amino acid sequences, is critical agonist for melanotropic activity.

This could be well explained by the mechanisms we mentioned above and is also consistent with Addisonian type pigmentation in which cortisone replacement therapy would decrease the ACTH level and significantly mitigate intensity of hyperpigmentation. On the other hand, we have already known that Addisons disease results in a significant higher level of ACTH compared with those of Graves disease. Therefore, it is reasonable the occurrence of hyperpigmentation in Addisons disease is much higher than that in Graves disease. The low morbidity of hyperpigmentation in hyperthyroidism may be due to multifactorial reasons and involves a complex genetic background. Different phenotypes of ACTH or their different affinity with MC-1R among individuals ultimately contribute to a variable sensibility to the effect of elevated ACTH in thyrotoxicosis condition. Although the increased ACTH can well explain the hyperthyroidism induced skin pigmentation, the differences of pigmentation distributions between hyperthyroidism and Addisons disease still needs further exploration. The simulating effect of anti-TSH receptor antibodies on epidermal melanocytes may partly take responsible for this difference, but we still cannot rule out other potential mechanisms for skin pigmentation in hyperthyroidism.

On the other hand, some researchers proposed that increased release of pituitary ACTH compensating for accelerated cortisol degeneration was responsible for the hyperpigmentation through increasing melanotropic activity.

We reviewed the pigmentation-related disease and discussed their distinct features compared with our case to further dissect the possible mechanism for hyperpigmentation accompanied by hyperthyroidism. The distribution of the pigmentation in our case is a bit different from that in Addisons disease which presents a diffuse pigmentation with a preferential occurrence on the mucous membranes and over pressure points, such as oral cavity, conjunctiva, and genitalia. As for Addisons disease, it gets overt high secretion of ACTH due to the deficient of adrenal cortex hormones.

In the case we present here, the pigmentation displayed good response to tretinoin and beta blocker treatment. As the euthyroidism was arrived, and ACTH levels came to normal, the hyperpigmentation significantly diminished.

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