Primary hyperparathyroidism and metastatic papillary carcinoma of the thyroid complicating a twin pregnancy

A Mohamad Safwan; KN Vijayan; Rakesh Chandru; S Aakash

doi:10.4103/ksj.ksj_35_22

CASE REPORT

Year : 2022 | Volume : 28 | Issue : 2 | Page : 190-193

Primary hyperparathyroidism and metastatic papillary carcinoma of the thyroid complicating a twin pregnancy

A Mohamad Safwan¹, KN Vijayan¹, Rakesh Chandru², S Aakash¹
¹ Department of General Surgery, KIMSHEALTH Hospital, Trivandrum, Kerala, India
² Department of Endocrine Surgery, Endocrine and Thyroid Care Centre, Nagercoil, Tamil Nadu, India

Date of Submission	11-Nov-2022
Date of Decision	03-Dec-2022
Date of Acceptance	22-Dec-2022
Date of Web Publication	30-Jan-2023

Correspondence Address:
Dr. A Mohamad Safwan
Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ksj.ksj_35_22

Abstract

Primary hyperparathyroidism (PHPT) is the unregulated overproduction of parathyroid hormone due to abnormal parathyroid gland which results in abnormal calcium homeostasis. PHPT in pregnancy is a rare and often unrecognised condition which possesses a threat to both the mother and the foetus. Papillary carcinoma of the thyroid is the most common thyroid malignancy and its management is quite challenging when it is diagnosed during pregnancy. Herewith, we report the case of a 28-year-old pregnant woman who presented with severe hyperemesis and hypercalcaemia due to PHPT along with incidentally detected metastatic papillary carcinoma thyroid complicating the pregnancy.

Keywords: Hyperparathyroidism, papillary carcinoma, parathyroid adenoma, pregnancy, thyroid malignancy

How to cite this article:
Safwan A M, Vijayan K N, Chandru R, Aakash S. Primary hyperparathyroidism and metastatic papillary carcinoma of the thyroid complicating a twin pregnancy. Kerala Surg J 2022;28:190-3

How to cite this URL:
Safwan A M, Vijayan K N, Chandru R, Aakash S. Primary hyperparathyroidism and metastatic papillary carcinoma of the thyroid complicating a twin pregnancy. Kerala Surg J [serial online] 2022 [cited 2023 Mar 25];28:190-3. Available from: http://www.keralasurgj.com/text.asp?2022/28/2/190/368592

Introduction

Primary hyperparathyroidism (PHPT) is characterised by hypercalcaemia with elevated or inappropriately normal parathyroid hormone (PTH) level due to parathyroid adenoma or parathyroid hyperplasia. PHPT in pregnancy is a rare disorder and usually unrecognised due to various confounding factors of pregnancy.^[1] The symptoms are usually non-specific as they overlap with the physiological changes seen during pregnancy. PHPT in pregnancy is associated with high maternal and foetal complications, reported in 67% and 80% of cases, respectively.^[2] Hence, early diagnosis and optimal treatment should be essential to reduce these complications.

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy which has a better prognosis both in pregnant and non-pregnant women. However, careful decision-making is necessary for a pregnant woman regarding the timing of surgery and post-operative management.

There are many anecdotal reports of PHPT in pregnancy and co-occurrence of PHPT and PTC. However, to the best of our knowledge, there are only two previous case reports in the world literature describing the complex association of PHPT and PTC in pregnancy.^[3],[4] Our case highlights the complex decision-making in the management of PHPT with severe hypercalcaemia and metastatic PTC in pregnancy.

Case Report

A 28-year-old woman in her 7 weeks of gestation was referred to our hospital with severe hyperemesis and dehydration. She had a history of treatment for infertility and recurrent abortions in the past, now conceived by the in vitro fertilisation technique. The abdominal ultrasonogram was within the normal limits with a viable twin gestation. On biochemical evaluation, she was found to have a normal thyroid function with a very high serum total calcium level of 18.4 mg/dl, low phosphorus level of 2 mg/dl and high parathormone (PTH) level of 684 pg/ml. She was diagnosed as a case of PHPT with severe hypercalcaemia complicating the pregnancy. Examination of the neck revealed a solitary nodule of size 2 cm × 1.5 cm in the region of the right lower pole of the thyroid with no cervical lymphadenopathy. There was no evidence of multiple endocrine neoplasia or hereditary syndromes.

She was admitted in a multidisciplinary intensive care unit and was managed aggressively with saline hydration and diuresis. Her calcium level decreased to 11.5 mg/dl, and she improved clinically over 48 h. The ultrasound of the neck revealed a nodule of size 2.5 cm × 1.8 cm × 1.5 cm at the left lower pole of the thyroid which was consistent with left parathyroid adenoma. The thyroid gland showed multiple small hypoechoic nodules of varying sizes with no suspicious features of malignancy and no evidence of cervical lymph nodes. Fine-needle aspiration cytology was performed from a thyroid nodule which showed the features of a benign colloid nodule.

She was planned for surgical removal of the parathyroid adenoma but was deferred considering the precious pregnancy and the risk of surgery during the first trimester. Alternatively, we performed radiofrequency (RF) ablation of the left inferior parathyroid adenoma under ultrasound guidance. Initially, a hydrodissection was performed with normal saline to prevent injury to the recurrent laryngeal nerve and carotid sheath. RF needle was placed into the lesion and ablated with a target temperature of 90° for 4 min. The post-procedure patient had temporary hoarseness of voice, and her calcium levels were normalised.

During follow-up after 6 weeks, she again developed hypercalcaemia (11.1 mg/dl) and hence planned for definitive surgery. Traditional four-gland exploration was performed, and we found a left inferior parathyroid lesion of size 1.5 cm × 1 cm × 1 cm with areas of adjacent necrosis and fibrosis which was excised [Figure 1].

Figure 1: Intraoperative image of the left inferior parathyroid adenoma

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Another small nodule near the left inferior pole of the thyroid was also excised. The intraoperative parathormone assay detects more than 50% drop in PTH levels 10 min after the excision of the lesion (pre-excision: 119 pg/ml; post-excision: 23 pg/ml), thus confirming the excision of the abnormal parathyroid gland. The post-operative period was uneventful, and the serum calcium levels were normal. Histopathological examination (HPE) confirmed the left inferior lesion to be a parathyroid adenoma [Figure 2], but surprisingly, the left-sided lesion was a lymph node with microscopic metastasis from papillary carcinoma thyroid. Hence, she was counselled for total thyroidectomy with central compartmental dissection which was performed during her post-partum period.

Figure 2: Histopathology of parathyroid adenoma showing chief cells and with absent stromal adipocyte

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The HPE showed a papillary microcarcinoma of size 0.6 cm with one metastatic lymph node. She was discharged with thyroxine suppression therapy and was kept under a regular follow-up. After 6 months, she had a normal calcium level, thyroglobulin level of 2 ng/ml, negative thyroglobulin antibodies and a normal neck ultrasonogram.

Discussion

The overall prevalence of PHPT is about 0.1%–0.4%, but exact data amongst pregnant women are lacking, with <200 cases described in the world literature.^[5] The majority of the cases are sporadic and most commonly due to a single adenoma in around 85% of cases, followed by hyperplasia in 15%–20% and parathyroid carcinoma in less than 1% of cases. The majority of the pregnant women with PHPT present at a later date with complications because the diagnosis at an early stage is often missed.^[6] This is because early symptoms of PHPT are being masked by the physiological changes of pregnancy such as low normal or low serum calcium due to hypoalbuminaemia, increased glomerular filtration rate and increased transplacental passage of calcium. In addition to these changes, the calcium-lowering effect of oestrogen leads to a reduction of total serum calcium levels. Hence, an ionised calcium level should be always measured for an accurate diagnosis.^[1],[7]

The maternal complications of hypercalcaemia are hyperemesis, pancreatitis, nephrolithiasis, muscle weakness, altered mental status, pre-eclampsia and hypercalcaemic crisis.^[8] The foetal complications are intrauterine growth restriction, low birth weight, preterm delivery and foetal demise.^[8] Neonatal hypocalcaemia with tetany and permanent hypoparathyroidism can also ensue.^[1] Most of the women with gestational PHPT remain unnoticed and may have repeated pregnancy losses. Our patient had a history of recurrent abortions but to justify PHPT as the cause remains uncertain. The diagnosis of PHPT is confirmed when there is an increase in serum ionised calcium and PTH levels. Familial hypocalciuric hypercalcaemia should be ruled out by quantifying low/normal 24-h urinary calcium, especially in younger individuals with mild hyperparathyroidism.

At present, there is no universal consensus regarding the optimal management of PHPT in pregnancy. The treatment options include conservative approach and surgery which should be tailored according to the severity of symptoms, degree of hypercalcaemia and foetal development.

Asymptomatic patients can be kept under active surveillance; however, recent data suggest that parathyroidectomy has a lower rate of pre-eclampsia and preterm labour compared to medical management.^[8],[9] Moreover, a review of the literature confirmed that both maternal and foetal complications are difficult to predict based on serum calcium levels, hence an early intervention rather than observation alone is appropriate.^[10],[6] Patients who are in a hypercalcaemic crisis are initially treated with saline hydration and diuresis, followed by urgent parathyroidectomy. There are insufficient data regarding the use of bisphosphonates and calcimimetics in pregnancy. Both these drugs cross the placenta and should be reserved for patients with life-threatening hypercalcemia.^[11]

Surgery is the only curative treatment, which can be safely performed during the second trimester.^[1],[7] Surgery should be avoided in the first trimester due to incomplete organogenesis along with the risk of teratogenicity due to anaesthetics and in the third trimester due to the risk of preterm labour. However, urgent parathyroidectomy is a definitive treatment in case of a hypercalcaemic crisis.^[1],[7]

The choice of surgery depends on the pre-operative localisation of the diseased gland. Ultrasonogram of the neck is the only localisation modality for PHPT in pregnancy because 99mTc-sestamibi scintigraphy and computed tomography neck are contraindicated due to the foetal risk of ionising radiation.^[12] Magnetic resonance imaging neck is safe, but it lacks sensitivity in localising small adenomas. Focused parathyroidectomy is always preferred; however, in case of failed pre-operative localisation, traditional four-gland exploration should be performed.^{[7],[12],[13]}

Surgery is the treatment of choice for papillary thyroid cancer diagnosed during pregnancy. Surgery can be safely performed during the second trimester, and it can also be deferred until puerperium in case of differentiated thyroid cancers except for those cancers with aggressive behaviour like a rapid enlarging tumour or extensive cervical nodal metastasis. Radioactive iodine (RAI) ablation is also contraindicated in pregnancy and during breastfeeding.^[14] Our patient had low-risk PTC, and hence, surgery was deferred until term and was performed during the puerperal period. RAI ablation was also avoided, and the patient was kept on thyroxine suppression therapy.

Conclusion

PHTP with papillary carcinoma of the thyroid in pregnancy is a rare association. PHPT in pregnancy is associated with high maternal and foetal complications. Hence, early diagnosis and prompt treatment are mandatory. Surgery should be ideally performed in the second trimester, but urgent parathyroidectomy is recommended in cases with maternal and fetal comprise occurs.

Patient consent

Consent was obtained from the patient.

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 understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Norman J, Politz D, Politz L. Hyperparathyroidism during pregnancy and the effect of rising calcium on pregnancy loss: A call for earlier intervention. Clin Endocrinol (Oxf) 2009;71:104-9.
2.	Kort KC, Schiller HJ, Numann PJ. Hyperparathyroidism and pregnancy. Am J Surg 1999;177:66-8.
3.	Arnez L, Lawrence V. Complex management decisions in a woman with concurrent primary hyperparathyroidism and metastatic papillary thyroid carcinoma, both presenting during pregnancy. Endocrinol Diabetes Metab Case Rep 2019;2019:19-0110.
4.	Baumann K, Weichert J, Krokowski M, Diedrich K, Banz-Jansen C. Coexistent parathyroid adenoma and thyroid papillary carcinoma in pregnancy. Arch Gynecol Obstet 2011;284:91-4.
5.	Dochez V, Ducarme G. Primary hyperparathyroidism during pregnancy. Arch Gynecol Obstet 2015;291:259-63.
6.	Schnatz PF, Curry SL. Primary hyperparathyroidism in pregnancy: Evidence-based management. Obstet Gynecol Surv 2002;57:365-76.
7.	DiMarco AN, Meeran K, Christakis I, Sodhi V, Nelson-Piercy C, Tolley NS, et al. Seventeen cases of primary hyperparathyroidism in pregnancy: A call for management guidelines. J Endocr Soc 2019;3:1009-21.
8.	McMullen TP, Learoyd DL, Williams DC, Sywak MS, Sidhu SB, Delbridge LW. Hyperparathyroidism in pregnancy: Options for localization and surgical therapy. World J Surg 2010;34:1811-6.
9.	Rigg J, Gilbertson E, Barrett HL, Britten FL, Lust K. Primary hyperparathyroidism in pregnancy: Maternofetal outcomes at a quaternary referral obstetric hospital, 2000 through 2015. J Clin Endocrinol Metab 2019;104:721-9.
10.	Kelly TR. Primary hyperparathyroidism during pregnancy. Surgery 1991;110:1028-33.
11.	Gonzalo García I, Robles Fradejas M, Martín Macías ML, Biain Ciganda A, Bustinza Beaskoetxea Z, Ruiz Pérez E, et al. Primary hyperparathyroidism in pregnancy treated with cinacalcet: A case report. J Obstet Gynaecol 2018;38:132-4.
12.	Walker A, Fraile JJ, Hubbard JG. “Parathyroidectomy in pregnancy” – A single centre experience with review of evidence and proposal for treatment algorithim. Gland Surg 2014;3:158-64.
13.	Stringer KM, Gough J, Gough IR. Primary hyperparathyroidism during pregnancy: Management by minimally invasive surgery based on ultrasound localization. ANZ J Surg 2017;87:E134-7.
14.	Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard Ba G, et al. Guidelines for the management of thyroid cancer. Clin Endocrinol 2014;81:1-22.