Primary hypothyroidism presenting as neuropsychiatric symptoms and pituitary enlargement in a young woman: illustrative case

Abstract

BACKGROUND

Pituitary adenomas are the most common cause of pituitary enlargement and can potentially warrant surgical intervention. However, there are physiological causes of pituitary enlargement that can be reversed with hormone replacement alone.

OBSERVATIONS

A 29-year-old female presented with acute onset paranoia to the psychiatry department. A computed tomography scan of the head revealed a 2.3 cm sellar mass with confirmation on magnetic resonance imaging. Testing showed a markedly elevated thyroid-stimulating hormone 1,600 µIU/mL (0.470–4.200 µIU/mL), suggesting pituitary hyperplasia. Treatment with levothyroxine replacement resulted in marked improvement in symptoms and resolution of pituitary hyperplasia on four month follow up.

LESSONS

This rare presentation of severe primary hypothyroidism highlights the importance of evaluating for physiological causes of pituitary enlargement.

Enlargement of the sellar contents in an adult patient is most often associated with neoplasia, with pituitary adenomas accounting for approximately 80%–90% of all such masses.^1,2 In fact there is a high prevalence of nonfunctioning, benign pituitary adenomas, the vast majority being microadenomas, reported in up to 20% in the general population.^2–4 Other pathological causes of pituitary enlargement include cysts, craniopharyngiomas, or meningiomas. However, physiological enlargement of the pituitary gland can also occur, stemming from several causes, notably pregnancy (lactotroph hyperplasia), puberty (gonadotroph and somatotroph hyperplasia), and primary hypothyroidism (thyrotroph hyperplasia).^1,5,6 For example, during pregnancy on average the pituitary doubles in size and can measure greater than one centimeter in cranio-caudad dimension.⁷ Pituitary imaging is not typically performed for these conditions in adults, so their frequency and extent is not known. Here we describe a case of pituitary hyperplasia from primary hypothyroidism with subsequent resolution after initiation of thyroid hormone replacement.

Illustrative Case

A healthy 29-year-old female presented to the emergency department with complaints of auditory hallucinations and paranoia for 1 week. She described hearing negative remarks by individuals who were not present. She otherwise described having chronic fatigue and irregular menstrual cycles for several years without other complaints. On physical examination, she was alert and oriented with normal vital signs. Slight periorbital edema was detected, and delayed relaxation phase of deep tendon reflexes was present. She was admitted to the psychiatric observation unit for further monitoring and evaluation.

On further evaluation, a computed tomography (CT) scan of the head revealed a sellar mass measuring 2.3 cm with extension into the cavernous sinus bilaterally and abutment of the optic chiasm. The neurosurgical consultant recommended a magnetic resonance imaging (MRI) of the pituitary with intravenous (IV) gadolinium contrast as well as full laboratory assessment of pituitary function. MRI revealed diffuse pituitary enlargement with homogeneous contrast enhancement but no discernable neoplasm (Fig. 1). The mass extended to the optic chiasm and cavernous sinus without displacement or invasion, respectively. Testing revealed normal electrolytes, prolactin, 114 ng/mL (reference range, 4.8–23.3 ng/mL); thyroid-stimulating hormone (TSH), 1,600 µIU/mL (0.470–4.200 µIU/mL); free thyroxine (FT₄), 0.25 ng/dL (0.80–1.70 ng/dL); cortisol, 25.4 µg/dL (6–18/4 µg/dL); insulin-like growth factor 1, 56 ng/mL (63–373 ng/mL); luteinizing hormone, <1.0 mIU/mL (2.5–12.5 mIU/mL); and follicle-stimulating hormone (FSH), 10.5 (3.5–14.5 mIU/mL). The patient was admitted to the medicine service and started on IV levothyroxine. Ophthalmology was consulted and confirmed no visual field deficits. She was transitioned to oral levothyroxine and discharged on 150 µg daily. During follow-up, the patient was adherent to her regimen with resolution of her symptoms. After 4 weeks, a repeat TSH level was normal at 4.070 µIU/mL along with a FT₄ of 1.76 ng/dL. Four months after initial MRI, repeat imaging showed complete resolution of the presumed pituitary hyperplasia (Fig. 2).

FIG. 1.

Initial MRI of the pituitary was performed because of pituitary enlargement noted on head CT. Images are coronal (left) and sagittal (right) gadolinium-enhanced T1-weighted magnetic resonance images. The pituitary was measured at 2.3 × 1.8 × 1.2 cm with extension into bilateral cavernous sinuses as well as abutment of the optic chiasm.

FIG. 2.

Repeat MRI of the pituitary 4 months after initiation of levothyroxine therapy, coronal (left) and sagittal (right) gadolinium-enhanced T1-weighted images. Compared to initial images, there is marked improvement in the pituitary hyperplasia.

Discussion

Observations

In the patient described above, pituitary enlargement was diffuse without any asymmetry or differential enhancement pattern that would suggest a neoplasm. This, in conjunction with the finding of a markedly elevated TSH level and concurrent low FT₄ makes a diagnosis of physiological pituitary hyperplasia (i.e., thyrotroph hyperplasia) from severe primary hypothyroidism highly likely. The diagnosis was confirmed by the subsequent shrinkage of the gland after normalization of both FT₄ and TSH following levothyroxine therapy. Of note, the mild hyperprolactinemia in this patient was likely the effect of stimulation from thyrotropin-releasing hormone on pituitary lactotrophs as opposed to either a prolactinoma or stalk compression. The latter is due to loss of dopaminergic inhibition of normal, tonic pituitary prolactin secretion by deviation of the infundibulum¹ with subsequent impairment of the flow of dopamine, a neurotransmitter that inhibits prolactin secretion, as seen with certain larger nonprolactinoma macroadenomas.

In the setting of physiological hyperplasia of the pituitary, it is recommended to treat the underlying cause. Lactotroph hyperplasia in pregnancy typically commences within the first few months of pregnancy and resolves several months postpartum.⁸ With primary hypothyroidism, the most common cause in the United States being Hashimoto thyroiditis, time to onset and resolution is unclear. One case series showed pituitary hyperplasia can occur as quickly as 3 to 5 weeks from the onset of primary hypothyroidism.⁹ Of the few case reports we could find, resolution of hyperplasia occurred between 4 and 10 months after initiation of thyroid hormone replacement,^10,11 but there are no comprehensive reports on the temporal, dynamic changes during the development and treatment of primary hypothyroidism.

There are only a few case reports within the literature demonstrating pituitary hyperplasia in primary hypothyroidism with subsequent resolution of pituitary enlargement after hormone replacement. Prior small studies have cited a prevalence of pituitary hyperplasia in up to 70% of cases in individuals with primary hypothyroidism.¹² However, studies are often small and described in young children and adolescents with TSH levels often close to 100 uIU/mL. Our case is unique in its degree of TSH elevation and confirmation of quick resolution of the patient’s pituitary enlargement after thyroid hormone replacement.

Lessons

This case highlights the importance of measuring and properly interpreting pituitary-related hormone concentrations in the evaluation of sellar abnormalities. Although macroadenomas are the most common etiology of large pituitary masses and are often treated by resection, physiological causes of pituitary enlargement may be under-recognized. Prompt identification, treatment, and close follow-up can led to resolution of hyperplasia and avoidance of unnecessary neurosurgical interventions.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Disclosures

Conception and design: Haider, Inzucchi. Acquisition of data: Haider, Templeton, Omay. Analysis and interpretation of data: Omay, Inzucchi. Drafting the article: Haider, Templeton. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors.