{"paper_id":"1beac4f2-bb37-4a5e-85e2-ebeb54a289ef","body_text":"Goserelin is a long-acting analogue of gonadotropinreleasing\nhormone (GnRH) which inhibits secretion\nof gonadotropin from the pituitary gland. 1  It does\nthis by reversible suppression of the release of\nluteinizing hormone (LH) and follicle-stimulating\nhormone (FSH) from the anterior pituitary gland. 2  The\nGnRH analogue has a greater affinity for its receptor,\nas high as 10-20 times. 3 , 4  As a treatment for endometriosis,\nit thins out the endometrial lining prior to\nablative therapy, and relieves pain and bleeding. 5  Few\ncases of goserelin-induced thyroiditis have been\npublished in medical literature. We present a report\nof a sodium pertechnetate Tc-99 m  thyroid scan with\nuptake inhibited by goserelin.\n\nA 42-year old woman presented to our department\nwith a two-year history of symptomatic toxic goitre.\nShe had bilateral proptosis, hyperhidrosis, heat\nintolerance, menstrual irregularity, weight loss despite\nhyperphagia and increased appetite, and more recently,\nhoarseness. She had no history of excessive\nconsumption of goitrogens. She had however grown\nup in a mountainous region of the country.\nHer main clinical findings were bilateral proptosis,\ngoitre, with no tracheal deviation, retrosternal extension\nnor palpably enlarged regional cervical lymph nodes.\nThere were no scalp swellings. She also had tachycardia\nof 96/min although her blood pressure was normal\nat 120/70 mmHg. An assessment of Graves’ disease\nwith thyroid-associated ophthalmopathy was made.\nPrior to her presentation, she had been commenced\non oral carbimazole 20 mg twice daily and atenolol\n25 mg daily.\nHer thyroid function test result, which had been done\ntwo weeks prior to her presentation, was consistent\nwith primary hyperthyroidism (see Table  1 ). Neck\nultrasound showed diffusely enlarged thyroid lobes,\nwith heterogeneous echotexture and minimal flow on\ncolour Doppler interrogation. A solitary sub-centimetre\nhypoechoic nodule was seen in the left lobe which\nshowed moderate flow on colour interrogation. The\nleft lobe was larger than the right (15.0 cm 3  and 11.9\ncm 3 , respectively) resulting in a combined volume of\n26.9 cm 3 . The overall impression was diffuse goitre\nwith a solitary left thyroid nodule.\nUltrasound-guided fine needle aspiration biopsy was\nconsidered for the nodule seen in the left lobe.\nHowever, its small size made successful biopsy unlikely.\nMoreover, repeat ultrasound three days showed no\nevidence of the nodule.\nShe had a technetium-99 m  pertechnetate (Tc-99 m  TcO 4 )\nthyroid scan after stopping carbimazole for five days.\nThe thyroid scan revealed generalised diminished\nuptake in the thyroid gland; which was relatively less\nthan salivary gland uptake. (See Figure  1 .) At this\nresolution, neither “hot” nor “cold” nodules could be\ndiscerned. However, there was an impression of\nextension of the thyroid gland inferiorly to the level\nof the sternal notch marker. Scan findings were\ndeemed suggestive of ongoing thyroiditis possibly\nsecondary to carbimazole use.\nShe was planned for an additional Tc-99 m  TcO 4  thyroid\nscan, after repeated counselling about foods to avoid.\nShe re-presented four days later for the thyroid scan;\nshe also had a repeat thyroid function test (Table  2 ).\nHowever, the repeat nuclear thyroid scan showed no\nimprovement, with persistent suboptimal uptake (see\nFigure  2 ). She then eventually disclosed a history of\nbeing on Zoladex® (goserelin) regimen for treatment of endometriosis. The treatment had commenced\nabout a year prior to her first thyroid scan, and almost\nthree years after the onset of hyperthyroid symptoms.\nThe image of the repeat technetium-99m pertechnetate\nthyroid scan is shown in Figure  2 .\nShe was thus found to be unsuitable for radioactive\niodine therapy at the time. Her management plan was\nfuture review with another Tc-99 m  TcO 4  thyroid scan\nonce she has finished her course of Zoladex®\ninjections. Thereafter, radioiactive iodine therapy would\nbe booked once thyroid scan uptake is satisfactory.\nHowever, she is yet to present for a follow-up Tc-99 m \nTcO4 thyroid scan.\n\nAs a therapeutic measure, goserelin has been associated\nwith quite a few adverse reactions and drug\ninteractions. 6  The World Health Organization\nVigiAccess database of adverse reactions reported\n8,805 reported side effects from goserelin at the time\nof writing this article. The highest occurrence of these\nreports was from Europe (52%) while a sparse 1%\noriginated from Africa. The modal age groups of\nthose affected were 18-44 and 45-64 years with a\nfrequency of 18%. Overall, the highest frequency was\nin those aged 18-75 years and above 75%.\nEndocrinologic side effects were 62 in number\n(0.007%). Of all endocrine reactions, 23 (0.003%) were\nthyroid-related. Specifically, hypothyroidism was\nreported in eight instances, and hyperthyroidism in\nseven. 7  Asides this, the literature is lacking about\ngoserelin effect on Tc-99 m  TcO 4  thyroid scan.\nThe subject of goserelin causing thyroid dysfunction has been investigated. Quite a few studies have shown evidence of its negative effect on thyroid function 7 – 9 . For instance, GnRH has been shown to significantly elevate thyroid-stimulating hormone (TSH) in women recipients 10 . On the other hand, it has also been linked to the development of Graves’ disease (GD) 9 .\nOestrogen affects thyroid function by causing an increase in serum thyroxine-binding globulin (TBG) concentrations due to increased sialylation of TBG. In this state, TBG has a slower hepatic clearance, which prolongs its half-life 11 , 12 . TBG bears more than 70% of bound thyroxine and triiodothyronine 13 . Furthermore, oestrogen receptors have been demonstrated in the developing foetal thyroid as well as in adult thyroid tissue 14 . The oestrogen component of contraceptive pills has been linked to the development of subclinical hypothyroidism 15 .\nGiven the premise that thyroid function is affected by oestrogen, it is plausible that oestrogen-deprived states may result in poorer thyroid function. That appears to have happened in this patient. The uptake of Tc-99 m  TcO 4  on the thyroid scan has been shown to vary with increasing levels of TSH, free thyroxine, free triiodothyronine, thyroid-stimulating antibodies, TSH-binding inhibitory immunoglobulin, and patient age 16 . The mechanism of goserelin inhibition of uptake of Tc-99 m  TcO4 has been deliberated. Onset of thyroid dysfunction following goserelin use is not immediate; reported instances start from one to four months after onset of treatment 17 . Thus, the cause of its side effects has been attributed to induced states of low oestrogen, rather than spikes of gonadotropin, in these patients. In addition, it was observed that goserelin did not seem to affect thyroid function in women without preexisting thyroid disease. However, it aggravated preexisting disease 18 . The spectrum of goserelin-induced thyroid disorders included hyperthyroidism, hypothyroidism and a mixture of both in affected individuals 17 – 19 .\nIn an attempt to allay the side effects experienced by patients, ‘add-back’ therapy has been described. This involves administering goserelin along with hormone replacement therapy for endometriosis 20 , 21 . It has served to provide symptomatic relief without reducing therapeutic outcome for such patients.\nWe recommend that patient preparation for nuclear thyroid scans and radioiodine treatment include enquiries about ongoing or prior GnRH therapy. Dysthyroid women receiving goserelin therapy will benefit from thyroid function monitoring. Randomised clinical trials are required to determine outcomes of thyroid function and thyroid scans in patients on GnRH analogues and those without.\n\nGoserelin-induced thyroiditis is a rare phenomenon;\nthe medical personnel caring for such patients need to\nbe aware of the possibility of its affecting thyroid\nfunction, leading to poor uptake on the pertechnetate\nthyroid scan.","source_license":"public-domain-us","license_restricted":false}