Large toxic multinodular goiter found in Asian woman with type 2 diabetes
A 39-year-old Vietnamese woman was referred to the endocrine clinic for the evaluation of a toxic multinodular goiter. The goiter was found after a routine physical exam by her new primary care physician.
The patient had no prior history of thyroid problems or head and neck radiation. Her family history was unremarkable for thyroid disease or cancer or pituitary problems.
Her thyroid function was tested, showing subclinical hyperthyroidism with thyroid-stimulating hormone <0.1 mIU/L, free thyroxine of 1.4 mcg/dL and total triiodothyronine of 156 ng/dL. Thyroperoxidase antibodies were negative, <0.5 IU/mL. Her PCP obtained a radioactive iodine (I-123) thyroid uptake that showed heterogeneous uptake in a large goiter that extended from the mandible to her sternal notch without nodules with increased or decreased uptake (Figure 1).
The right lobe measured 9 cm x 4 cm, and the left lobe measured 10 cm x 5 cm (expected lobe size, 5 cm x 2 cm). The thyroid uptake at 5.6 hours was 25% (expected, 5%-15%). She was referred to endocrinology for management.
‘Thick spade-like fingers’
She was a small Asian female with a marked enlarged visible goiter but with mild prognathia and thick spade-like fingers. She denied, via an interpreter, that her face or hands had changed in appearance. A family member confirmed her appearance had not changed in years. They were not able to provide pictures of her from the past.
She denied any thyroid-related symptoms, including dysphagia, neck mass, palpitations, weight loss or anxiety. She was recently diagnosed with type 2 diabetes, without polyuria or polydipsia. Her diabetes was in good control with metformin and glipizide with an HbA1c of 6.5%.
Her physical exam was significant for a small, slim Asian female with a 70-g to 80-g soft goiter without discrete nodules and a negative Pemberton’s sign suggesting no thoracic outlet obstruction. She had a prominent jaw but without increase spacing between teeth or malocclusion. She had no skin tags.
Her hands were disproportionately large with thickened fingers and increase soft tissue thickness of her palms. Thyroid tests were repeated and remained with subclinical hyperthyroidism.
Elevated GH, IGF-I levels
She had an elevated growth hormone level of 14.8 ng/mL (normal adult female: <10 ng/mL) and insulin growth factor I of 850 ng/mL (normal: 90 ng/mL-360 ng/mL), consistent with acromegaly. At her next visit, her other pituitary hormones were normal, including prolactin 7.2 ng/mL, adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone and cortisol.
An MRI of the pituitary with gadolinium contrast with slices through the hypothalamus and pituitary revealed a 13-mm x 11-mm x 9-mm (anterior-posterior-by-transverse-by-craniocaudal) mass in the left side of the pituitary that did not enhance with gadolinium, all consistent with a pituitary adenoma (Figure 2).
She was started on methimazole 5 mg daily and referred to neurosurgery for resection of the pituitary macroadenoma and acromegaly. She was cured by a transsphenoidal resection of the left-sided tumor.
Three months after resection, her GH was 2.1 ng/mL (normal adult female: <10 ng/mL) and her IFG-I was <6 ng/mL (normal: 90-360 ng/mL). Although she remained hyperthyroid from her toxic multinodular goiter, her thyroid functions were normal on methimazole 5 mg daily and her anterior and posterior hormone functions were normal. In fact, she had an unintentional uneventful pregnancy within 6 months of her pituitary surgery.
Excess GH secreted from pituitary adenoma increases circulating IGF-I from the liver. The elevated IGF-I stimulates growth of tissue and results in the physical stigmata of gigantism before puberty and acromegaly after puberty.
This distinction reflects the differential effect of IFG-I on the long and membranous bones. Excess IGF in the young will allow proportional growth of all bones and gigantism.
After fusion of the growth plates of long bones during puberty induced by sex steroids, the long bones cannot grow, but there is continued growth of the membranous bones in the forehead and mandible, resulting in the prominent supraorbital ridge and prognathia typical of acromegaly.
Other growth responses to acromegaly include all soft tissues, resulting in thickened fingers, increase palmar and heel pad thickness, skin tags and colon polyps with increased risk for colon cancer. Excessive growth of the tongue, lips, nose and retropharyngeal tissues increase the risk for sleep apnea.
Untreated acromegaly will cause enlargement of the heart with statistically significant increased risk for cardiovascular events and mortality. IFG-I is a growth factor for the thyroid resulting in a diffuse goiter enlargement that can be accompanied with adenomatous nodules and the development of a toxic multinodular goiter (TMNG).
Fortuitously for this patient, the combination of large hands, prominent jaw, recent diagnosis of type 2 diabetes and adenomatous goiter brought the diagnosis of acromegaly at an early stage that allowed a surgical cure. It is important during the routine evaluation of a common problem such as a goiter that other causes besides familial goiter, iodine deficiency and radiation exposure should be considered — including acromegaly.