Dermatologic Manifestations of Multiple Endocrine Neoplasia Type 1

Introduction

Multiple endocrine neoplasias type 1 is an uncommon endocrine disorder characterized by developing tumors on various endocrine glands. Apart from the different systemic signs and symptoms, the condition is associated with several skin lesions. These skin lesions are the dermatological manifestations of multiple endocrine neoplasia type 1. Some of these skin lesions are unique to the condition, whereas some are prevalent in the general population and associated with other diseases. The extent and recurrence of lesions and general treatment of the condition determine the treatment and prognosis of these skin lesions.

What Is Multiple Endocrine Neoplasia Type 1?

Multiple endocrine neoplasias or MEN 1 syndrome is a rare endocrine disorder caused due to genetic mutations (variations). The condition is marked by the development of several tumors from cells of particular neuroendocrine tissues. The endocrine system is a critical system of the body consisting of endocrine glands, hormones, and receptors. These three components work harmoniously to carry out various vital functions of the body. In people affected by multiple endocrine neoplasia type 1, tumors are developed in several endocrine glands. The parathyroid glands, gastro-entero-pancreatic tract, and pituitary gland are the most commonly affected endocrine glands in people with multiple endocrine neoplasia type 1. These affected glands release excessive hormones into the bloodstream, which can cause several symptoms and associated medical conditions. In addition, some of the tumors developing in multiple endocrine neoplasia are malignant (cancerous).

What Causes Multiple Endocrine Neoplasia Type 1?

• Multiple endocrine neoplasia type 1 is an uncommon genetic condition due to MEN1 gene mutations.

• Nuclear protein menin is encoded by the MEN1 gene. However, menin's precise function has yet to be entirely discovered.

• The MEN1 gene is supposedly a tumor suppressor gene. Therefore, it is responsible for several functions, including regulating cell division, repairing and replicating DNA, and apoptosis (the normal process of signaling the cells to die).

• Specific cells may continue to grow and multiply due to malfunctioning tumor suppressor genes, leading to the development of tumors.

• The affected person may get this genetic alteration as a new gene mutation or inherit it in an autosomal dominant form (when just one copy of a mutated gene is required for the disease to manifest).

Symptoms of Multiple Endocrine Neoplasia Type 1

Multiple endocrine neoplasia type 1 symptom can vary depending on which glands are affected by tissue overgrowth or tumor formation. The development of a tumor makes the affected glands overactive and causes them to release excessive amounts of hormones. These elevated levels of hormones are the primary factors for developing symptoms in the case of multiple endocrine neoplasias 1. The general symptoms of multiple endocrine neoplasias include:

• Tiredness.

• Pain in the bones.

• Easily breakable or broken bones.

• Kidney stones.

• Stomach or intestinal ulcers.

• Muscle weakness.

• Frequent urination.

• Increased thirst.

• Depression.

• Digestive problems.

• Constipation.

• Acid reflux.

• Abdominal pain.

• Low blood sugar levels.

• Swollen hands and feet.

• Skin lesions like angiofibromas, collegenomas, lipomas, etc.

What Are the Dermatological Manifestation of Multiple Endocrine Neoplasia Type 1?

Dermatological manifestations are the manifestations or symptoms seen on the skin. It can also be called skin lesions or cutaneous lesions. In addition, a non-dermatological disorder's cutaneous signs, symptoms, or physiological changes are called skin manifestations. Various skin lesions seen in the case of multiple endocrine neoplasia type 1 are:

• Angiofibromas.

• Collegenomas.

• Melanosism Guttaca.

• Lipomas.

• Cafe au lait macules.

What Are Angiofibromas?

• Angiofibromas are papules (a small pimple or swelling of the skin) that may be skin-colored, light pink, or brown.

• These papules are typically 1 mm to 4 mm in diameter and are characterized by the presence of small and wide blood vessels on the skin.

• In the case of angiofibroma, approximately two to 50 lesions may be seen on the skin.

• The majority of these lesions are located in the center of the face.

• Angiofibroma is reported in 5 % to 88 % of the patients with multiple endocrine neoplasia type 1.

• Additionally, multiple endocrine neoplasia type 1 patient frequently have angiofibroma on their upper lip and vermillion lip border (demarcation between the lip and normal skin).

• Angiofibroma appears during the second decade of life in patients with multiple endocrine neoplasias type 1.

What Are Collagenomas?

• Collagenomas are either less pigmented or skin-colored skin lesions seen in the case of multiple endocrine neoplasia type 1.

• Collagenoma is firm, and it may be round or oval.

• A collagenoma may be 0.2 cm to 2 cm in diameter.

• There may be several smaller lesions or a few larger lesions present.

• Most collagenomas are seen on the neck and upper region of the trunk.

• About 72 % of multiple endocrine neoplasia patients will develop collagenomas, and 83 % to 93 % will have numerous lesions.

What Are Lipomas?

• Lipomas are nodules (small round lumps) that are soft and compressible.

• Lipomas are present subcutaneously, which means they are present just under the skin.

• These lesions are typically 0.5 cm to 5 cm in diameter.

• Lipomas may be present as solitary lesions or as multiple lesions.

• Lipomas are commonly seen in the body's scalp, trunk, and extremities.

• Lipomas have been seen in about 3 % to 34 % of individuals with multiple endocrine neoplasia type 1.

What Are Melanomas?

• Melanomas are skin lesions developing in the melanocytes. These melanocytes are melanin-forming cells responsible for the pigmentation of the skin.

• Melanomas are malignant or cancerous.

• Apart from manifesting on the skin, melanomas can also occur in the eyes, and rarely can they occur inside the nose or throat.

What Are Cafe AU Lait Macules?

• Cafe au lait macules are flat and pigmented skin lesions. They are typically light brown to dark brown in color and well-circumscribed.

• Because they are prevalent in the general population, café au lait macules should not be employed as a marker for multiple endocrine neoplasias.

• Patients with multiple endocrine neoplasias have been seen to develop café au lait macules that are three or fewer in number.

• Cafe au lait macules may be present at birth, or they can develop in the early stages of life and range in size from a few millimeters to several centimeters.

Conclusion

Multiple facial lipomas, collagenomas, and angiofibroma alone do not constitute a diagnosis of multiple endocrine neoplasia type 1. However, these skin lesions need more testing for multiple endocrine neoplasia type 1, including imaging investigations to check for tumors and blood tests to look for hormone hypersecretion. Subcutaneous lipomas may be surgically removed for aesthetic reasons; they normally do not recur. Angiofibromas and collagenomas generally do not require any treatment.