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CASE REPORT
Year : 2020  |  Volume : 17  |  Issue : 1  |  Page : 19-21

Vanishing pituitary macroprolactinoma and secondary hypothyroidism due to pituitary apoplexy


1 Department of Endocrinology, Center for Endocrinology Diabetes Arthritis and Rheumatism (CEDAR) Superspeciality Clinics, New Delhi, India
2 Department of Rheumatology and Immunology, Center for Endocrinology Diabetes Arthritis and Rheumatism (CEDAR) Superspeciality Clinics, New Delhi, India
3 Department of Endocrinology, CEDAR Superspeciality Clinics, Bengaluru, Karnataka, India
4 Department of Endocrinology, CEDAR Superspeciality Clinics, Zirakpur, Punjab, India

Date of Submission11-Mar-2020
Date of Acceptance11-Mar-2020
Date of Web Publication24-Apr-2020

Correspondence Address:
Dr. Deep Dutta
Department of Endocrinology, Center for Endocrinology Diabetes Arthritis and Rheumatism Superspeciality Clinics, 33 Netaji Subhash, Pocket-1, Phase-2, Sector 13, Dwarka, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_11_20

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  Abstract 


Macroprolactinomas usually need long-term cabergoline therapy, often lifelong, as complete resolution of these tumors is rare. We present a vanishing pituitary macroprolactinoma which evolved into a complete empty sella following 2 years of cabergoline therapy. A 17-year-old girl with primary amenorrhea, chronic headache, and galactorrhea for 2 months was diagnosed to have pituitary macroprolactinoma (20 mm × 17 mm × 16 mm; prolactin 451 ng/ml). T2-weighted imaging revealed fluid level in adenoma suggestive of bleed in the tumor suggestive of pituitary apoplexy. Cabergoline was initiated at 0.5 mg/week and was uptitrated to 3 mg/week over 6 months to ensure prolactin was suppressed. Magnetic resonance imaging pituitary after 2 years of cabergoline therapy revealed empty sella with pituitary stalk traced till the floor of sella turcica, without any evidence of adenoma. Hormone evaluation revealed low total T4 levels (5.1 mcg/dl); low thyroid-stimulating hormone (0.9 mIU/L); normal morning cortisol (18.1 mcg/dl); and normal prolactin (4 ng/ml), leading to the diagnosis of secondary hypothyroidism. Cabergoline dose was tapered gradually. Levothyroxine replacement was started at 50 mcg/day. Pituitary apoplexy and associated infarction 2 years back lead to ischemic necrosis in adenoma, leading to its spontaneous resolution in our patient. The adenoma had damaged adjacent normal pituitary cells due to limited space in sella, resulting in empty sella. Pituitary apoplexy is nature's way of curing pituitary adenoma. Complete disappearance of adenoma and the resulting empty sella syndrome are the novelty of this report.

Keywords: Apoplexy, empty sella syndrome, macroprolactinoma, pituitary macroadenoma, secondary hypothyroidism


How to cite this article:
Dutta D, Sharma M, Shivaprasad K S, Kumar M. Vanishing pituitary macroprolactinoma and secondary hypothyroidism due to pituitary apoplexy. Thyroid Res Pract 2020;17:19-21

How to cite this URL:
Dutta D, Sharma M, Shivaprasad K S, Kumar M. Vanishing pituitary macroprolactinoma and secondary hypothyroidism due to pituitary apoplexy. Thyroid Res Pract [serial online] 2020 [cited 2020 Dec 5];17:19-21. Available from: https://www.thetrp.net/text.asp?2020/17/1/19/283214




  Introduction Top


Drug-induced hyperprolactinemia followed by uncontrolled subclinical and primary hypothyroidism is the most common cause for raised prolactin levels.[1],[2] Prolactinomas constitute <1% of all patients with raised prolactin levels but are the most common pituitary tumors.[3] Dopaminergic (DA) agonists (cabergoline) are the treatment of choice for both microprolactinomas and marcoprolactinomas, except in the setting of sight-threatening pituitary macroprolactinoma being present compressing the optic chiasma, which may warrant a decompressing pituitary surgery.[4] DA agonists therapy for macroprolactinomas is usually for lifelong as complete resolution and disappearance of the tumors are extremely rare, in contrast to around 2 years therapy needed for complete resolution of microprolactinomas.[5] Empty sella has been reported as a very rare complication of chronic DA therapy.[3],[6],[7] We present a vanishing pituitary macroprolactinoma which evolved into a complete empty sella following 2 years of cabergoline therapy. Pituitary apoplexy at the time of diagnosis contributed to the vanishing pituitary macroadenoma.


  Case Report Top


A 17-year-old girl with primary amenorrhea, chronic headache, and galactorrhea for 2 months was diagnosed to have pituitary macroadenoma (20 mm × 17 mm × 16 mm) with contrast uptake seen only in the rim of the pituitary on magnetic resonance imaging (MRI) brain [Figure 1]a and [Figure 1]b. T2-weighted imaging revealed fluid level in adenoma suggestive of bleed in tumor [pituitary apoplexy; [Figure 1]c. Biochemical evaluation was significant for hyperprolactinemia (451 ng/ml), euthyroidism, eucortisolism, and normal insulin-like growth factor-1, leading to diagnosis of macroprolactinoma. Cabergoline was initiated at 0.5 mg/week and was uptitrated to 3 mg/week over 6 months to ensure prolactin was suppressed. Prolactin levels was monitored 3-monthly. Anterior and posterior pituitary hormones were monitored annually.
Figure 1: (a) T1-weighted magnetic resonance imaging pituitary lateral view (2017) showing 20 mm × 17 mm × 16 mm pituitary adenoma with contrast enhancement only in the peripheral rim (white arrow). The adenoma has a significant suprasellar component and is compressing the optic chiasma. (b) T1-weighted magnetic resonance imaging pituitary coronal view (2017) showing pituitary macroadenoma with peripheral contrast enhancement and compression of the optic chiasma (white arrow). (c) T2-weighted magnetic resonance imaging pituitary lateral view (2017) showing fluid level (white arrow) suggestive of bleed in the pituitary adenoma due to apoplexy. (d) T1-weighted magnetic resonance imaging pituitary lateral view (2020) showing empty sella with a thin rim of pituitary seen lining the sella (white arrow). (e) T1-weighted magnetic resonance imaging pituitary coronal view (2020) showing empty sella with herniation of the optic chiasma in the sella. (f) T1-weighted magnetic resonance imaging pituitary coronal view (2020) showing empty sella with pituitary stalk traced till the floor of the sella (white arrow)

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MRI pituitary after 2 years of cabergoline therapy revealed empty sella with pituitary stalk traced till the floor of the sella turcica [Figure 1]d, [Figure 1]e, [Figure 1]f. There was no evidence of adenoma. The patient was clinically asymptomatic. Hormone evaluation revealed low total T4 levels (5.1 mcg/dl; normal 6.4–14 mcg/dl); low thyroid-stimulating hormone (0.9 mIU/L; normal 0.45–5.1 mIU/L); normal morning cortisol (18.1 mcg/dl); normal prolactin (4 ng/ml); normal luteinizing hormone (1.2 mIU/ml); and follicle stimulating hormone (2.3 mIU/ml) levels, leading to the diagnosis of secondary hypothyroidism. Cabergoline dose was tapered gradually. Levothyroxine replacement was started at 50 mcg/day. The patient had normal vision. The patient was counseled for regular periodic follow-up 3-monthly to screen for secondary hypocortisolism and hypogonadism.


  Discussion Top


In a cohort of 176 patients with macroprolactinoma from Russia on DA therapy, in one patient (0.6%), visual deterioration was noted secondary to optic chiasma dislocation following the development of empty sella.[6] In another three patients (1.7%), intratumoral hemorrhage with cystic transformation was noted.[6] Jones et al. reported seven patients who developed secondary vision loss due to optic chiasma herniation secondary to pituitary shrinkage following DA therapy for macroprolactinoma, which had resulted in partial-to-complete empty sella.[6] The duration of DA therapy ranged from 4 months to 10 years.[7] Six of these patients were on bromocriptine, while one was on cabergoline. Pituitary apoplexy was ruled out in all the patients.[7]

Hypopituitarism has been noted in up to 53% of macroprolactinomas at the time of initial diagnosis.[8] Recovery of pituitary function (growth hormone axis and adrenocorticotrophic hormone axis) has been noted following DA therapy in up to 60% of patients with macroprolactinoma and hypopituitarism at the time of initial diagnosis.[8] Our patient, however, had normal pituitary hormone functions at the time of diagnosis of macroprolactinoma.

Sella being a bony cage with limited space, any pathology which involves enlargement of one or more of the pituitary cells, is a risk factor for damage to adjacent other normal pituitary cells, which can lead to deficiency of one or more of the pituitary–end gland axis. This explains which a simple and easily treatable condition like primary hypothyroidism, when left untreated, can lead to chronic persistent hypertrophy of thyrotrophs in the sella, which can damage the adjacent other pituitary cells, leading to the development of panhypopituitarism.[9]

Cabergoline therapy is a risk factor for pituitary apoplexy. Further, macroprolactinomas, especially the rapidly growing ones, are at a risk of apoplexy due to aberrant blood supply in the pituitary tumor. In a cohort of 368 patients with prolactinoma from England, pituitary hemorrhage was documented in 25 patients (6.8%), which higher rates being in macroprolactinoma (20.3%) as compared to only 3.1% in microprolactinoma.[10] Of these, only three patients had classical pituitary apoplexy. The other 22 patients had a complete spontaneous resolution of pituitary hemorrhage over 26.6 ± 23.3 months, with conservative management on DA therapy.[10] Pituitary apoplexy in macroprolactinomas has been linked with cerebrovascular accidents in both children and adults.[11],[12]

Pituitary apoplexy and associated infarction 2 years back lead to ischemic necrosis in adenoma, leading to its spontaneous resolution in our patient. The adenoma had damaged adjacent normal pituitary cells due to limited space in sella, resulting in empty sella. Pituitary apoplexy is nature's way of curing pituitary adenoma. Complete disappearance of adenoma and the resulting empty sella syndrome are the novelty of this report. Our patient has developed secondary hypothyroidism. She did not notice vision abnormalities as has been seen in few of the reports above. MRI pituitary showed normally localized optic chiasma in her. Defect of any of the hypothalamic–pituitary–end gland axis system is a risk factor for future defects in other pituitary hormone axis. Hence, patients with apoplexy warrant periodic pituitary hormone assessment to rule out panhypopituitarism in the future.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sharma LK, Sharma N, Gadpayle AK, Dutta D. Prevalence and predictors of hyperprolactinemia in subclinical hypothyroidism. Eur J Intern Med 2016;35:106-10.  Back to cited text no. 1
    
2.
Sharma N, Dutta D, Sharma LK. Hyperprolactinemia in Children with Subclinical Hypothyroidism. J Clin Res Pediatr Endocrinol 2017;9:350-4.  Back to cited text no. 2
    
3.
Selvan C, Dutta D, Ghosh S, Mukhopadhyay S, Chowdhury S. Growth hormone deficiency, secondary hypothyroidism, and empty sella following treatment of childhood macroprolactinoma. Indian J Endocrinol Metab 2013;17:S132-4.  Back to cited text no. 3
    
4.
Dutta D, Ghosh S, Mukhopadhyay S, Chowdhury S. Rapid reduction with cystic transformation of invasive giant prolactinoma following short term low dose cabergoline. Indian J Endocrinol Metab 2012;16:1048-51.  Back to cited text no. 4
    
5.
Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, et al. Diagnosis and treatment of hyperprolactinemia: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:273-88.  Back to cited text no. 5
    
6.
Astaf'eva LI, Kadashev BA, Kutin MA, Kalinin PL. Complications of treatment of prolactinoma by dopamine agonists. Zh Vopr Neirokhir Im N N Burdenko 2011;75:41-50.  Back to cited text no. 6
    
7.
Jones SE, James RA, Hall K, Kendall-Taylor P. Optic chiasmal herniation--an under recognized complication of dopamine agonist therapy for macroprolactinoma. Clin Endocrinol (Oxf) 2000;53:529-34.  Back to cited text no. 7
    
8.
Colao A, Di Sarno A, Landi ML, Cirillo S, Sarnacchiaro F, Facciolli G, et al. Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 1997;82:3574-9.  Back to cited text no. 8
    
9.
Dutta D, Maisnam I, Ghosh S, Mukhopadhyay P, Mukhopadhyay S, Chowdhury S. Panhypopituitarism with empty sella a sequel of pituitary hyperplasia due to chronic primary hypothyroidism. Indian J Endocrinol Metab 2012;16:S282-4.  Back to cited text no. 9
    
10.
Sarwar KN, Huda MS, Van de Velde V, Hopkins L, Luck S, Preston R, et al. The prevalence and natural history of pituitary hemorrhage in prolactinoma. J Clin Endocrinol Metab 2013;98:2362-7.  Back to cited text no. 10
    
11.
Kasl RA, Hughes J, Burrows AM, Meyer FB. Pediatric ischemic stroke from an apoplectic prolactinoma. Childs Nerv Syst 2015;31:1387-92.  Back to cited text no. 11
    
12.
Navarro-Bonnet J, Martínez-Anda JJ, Balderrama-Soto A, Pérez-Reyes SP, Pérez-Neri I, Portocarrero-Ortiz L. Stroke associated with pituitary apoplexy in a giant prolactinoma: A case report. Clin Neurol Neurosurg 2014;116:101-3.  Back to cited text no. 12
    


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