Endocrine and Thyroid Cancers Overview

Endocrine Cancers Overview

• Cancers of the endocrine system are rare, representing 3.1% of all cancers as of 2020
• Thyroid cancer accounts for 95% of endocrine cancer cases
• The majority of non-thyroid endocrine cancers are rare, with fewer than 6 cases per 100,000 yearly
• Endocrine tumors can be difficult to identify and complex to treat due to the lack of clinical symptoms

Thyroid Cancer Statistics

• The 5th most common cancer in women
• In the US, in 2020, there were approximately 52,890 new cases of thyroid carcinoma, accounting for 2.9% of all new cancer cases
• The rate of death from thyroid cancer has been stable at 0.4%
• The median age of diagnosis ranges from 45-50 years
• Thyroid cancer is 2-4 times more common in women than in men
• 5-year relative survival rate is about 98%

Risk Factors for Thyroid Cancer

• Advancing age
• Female sex
• Exposure to radiation as a child, whether from cancer treatment or nuclear accidents
• A family history of thyroid cancer or hereditary syndromes, including MEN 2A and 2B, FAP, Carney Complex, Werner syndrome and Cowden syndrome
• Thyroid nodules are benign in approximately 90% of cases, and 95% of individuals are asymptomatic

Clinical Features & Diagnosis of Thyroid Cancer

• Most thyroid cancer patients have normal thyroid function tests
• An initial evaluation should include measuring TSH levels
• If TSH is low, a radioactive iodine scan should be conducted
• Hyperfunctioning nodules are rarely malignant
• Physical examinations or imaging may reveal thyroid nodules
• Thyroid nodules may cause an enlarged neck mass, hoarseness, dysphagia, or concerns with swallowing
• Suspicious sonographic features are nodules that are hypoechoic, have an irregular border, and show microcalcifications
• Fine-needle aspiration serves as the primary diagnostic tool

Thyroid Fine Needle Aspiration Bethesda Classification

• Nondiagnostic
• Benign
• Atypia of undetermined significance or follicular lesion of undetermined significance
• Follicular neoplasm
• Suspicious for malignancy
• Malignant

Goals of Initial Treatment for Thyroid Cancer

• Implement adequate surgery
• The extent of surgery and the surgeon's experience are important in managing potential surgical complications
• Use RAI treatment and TSH suppression
• Properly stage and risk stratify the disease to determine prognosis, disease management, and follow-up

Thyroid Cancer Types & Classifications

• Follicular cells produce thyroid hormones
• Parafollicular C-cells produce calcitonin

Types Originating From Follicular Cells

• Differentiated: Papillary and Follicular type
• Accounts for more than 90% of thyroid cancers
• Papillary carcinoma in 60%-70% of cases
• Follicular carcinoma accounts for 15%-20% of cases
• Undifferentiated: Anaplastic

Other Classifications

• Originating from C cells: Medullary Thyroid Cancer
• Medullary and anaplastic forms are more aggressive and more likely to metastasize

Thyroid Cancer Prognosis

• Post-surgery, the pathology and imaging define whether the risk of recurrence is low, intermediate, or high
• This determines the need for radioactive iodine ablation and the level to which TSH should be suppressed
• Thyroglobulin serves as a marker of recurrence
• Perform regular physical exams and neck ultrasounds

Medullary Thyroid Cancer (MTC)

• Originates from parafollicular calcitonin-secreting C-cells
• Comprises 1%-2% of thyroid cancers
• Familial in 25% of cases, resulting from either MEN2A or MEN2B syndromes
• Inherited in an autosomal dominant fashion and result from mutations in the RET proto-oncogene
• Prophylactic thyroidectomy can prevent MTC in at-risk individuals
• Calcitonin is the most important tumor marker

Childhood Thyroid Cancer

• Children most frequently get Papillary and Follicular thyroid cancer
• Radiation to the neck and external radiation exposure are risk factors
• Advanced disease, multifocal tumors with involvement in the lymph node and extrathyroidal disease are common presentations
• Children have a very good prognosis and high rate of cure
• Treatment includes thyroidectomy, radioactive iodine, and TSH suppression

Multiple Endocrine Neoplasia (MEN)

• Consist of disorders involving two or more endocrine glands
• Typically inherited in an autosomal dominant pattern
• Can manifest as benign and malignant tumors
• Tumors may be functional or nonfunctional
• There are 3 types of MEN based on the combinations of endocrine tumors involved

Multiple Endocrine Neoplasia Type 1

• Also called Wermer Syndrome
• Mutation in the MEN1 gene at 11q13 encodes for menin (tumor suppressor protein)
• Organs affected (the 3 Ps):
  • Pituitary: Most common type is prolactinoma, present in 15-50% of cases
  • Parathyroid: Hyperplasia or adenoma in 95% of cases
  • Pancreas: Tumors are aggressive and multifocal, including gastrinoma, insulinoma, and glucagonoma, present in 30-80% of cases
• Majority of tumors are benign, while malignant tumors target pancreatic islets
• Hyperparathyroidism is often one of the first indicators
• Symptoms include elevated calcium, kidney stones, peptic ulcer disease and hypopituitarism

Multiple Endocrine Neoplasia Type 2A

• Subdivided into two syndromes: MEN2A (95% of cases) and MEN2B
• MEN 2A is characterized by medullary thyroid cancer, pheochromocytoma, and parathyroid tumors
• Mutation involves the RET proto-oncogene
• Further classified into four variants:
• Classical MEN2A, the most common
• MEN2A with cutaneous lichen amyloidosis (CLA)
• MEN2A with Hirschsprung disease (HSCR)
• Familial medullary thyroid cancer (FMTC)
• Intervention requires prophylactic thyroidectomy as a child
• Regular biochemical screening for pheochromocytoma and hyperparathyroidism is needed in the teen years

Multiple Endocrine Neoplasia Type 2B

• Distinguished by Medullary Thyroid Cancer and Pheochromocytoma
• RET proto-oncogene mutation is different from MEN2a
• MTC presentation occurs earlier in life and is more aggressive
• Pheochromocytoma present in 50% of cases
• Hyperparathyroidism does not develop
• Exhibits ganglioneuromas and marfanoid habitus

Adrenal Carcinoma

• Rare
• Incidence is two per million
• Incidence peaks
• Children less than 5 years old
• Adults between 40 to 50 years
• Childhood cancers
• 1.3% are adrenal carcinoma
• 0.02%–0.2% of adult cancers
• Occurrences
• Women account for two-thirds
• Median overall survival is 3–4 years
• Tumors
• Majority are sporadic
• Occasionally
• Hereditary syndromes
• Children - MEN1 - Li-Fraumeni syndrome - Beckwith–Wiedemann syndrome - Lynch syndrome

Adrenal Carcinoma Signs & Symptoms

• Nonfunctioning tumors patients
  • Abdominal masses
• Abdominal pain
• Weight loss
• Fullness
• Indigestion
• Nausea
• Vomiting
• Pain
• Weakness
• Imaging procedures reveals 20-30% of adrenal tumors
• Functioning tumors patients
• Nonfunctioning tumor symptoms
• Excess hormone symptoms
• 40%–60% patients at presentation
• hypercortisolism (Cushing syndrome)
• 50%–70% of hormone-secreting ACC patients
• Androgen excess (virilization)
• 20%–30% of female patients
• Estrogen excess (feminization)
• 5% of male patients
• mineralocorticoid excess
• 2%–3% of patients

Adrenal Tumors

• Radiological Studies
• Incidental findings are adrenal tumors
• Large tumors
• Greater than 4–6 cm
• Tumor growth
• Increasing over a 6-month period
• Carcinoma
• Nodules
• Units above 20 hounsefield
• Heterogeneous
• Areas of necrosis
• Tumors
• Bilateral
• 2%–10% of cases

Differentiating Adrenocortical Cancer

• Use Weiss criteria to distinguish adrenocortical cancer from adrenocortical adenoma
• Specific immunohistochemical studies
• Adrenocortical carcinoma should have three or more of the findings
• High nuclear grade,
• Eosinophilic cytoplasm (more than 75%),
• Diffuse architecture (more than 33%),
• Necrosis,
• Mitotic figures (more than 5/50 high power field (HPF),
• Atypical mitotic figures,
• Capsular invasion, vascular invasion, and sinusoidal invasion
• MIB-1/Ki-67 is helpful tool
• Assessment of benign versus borderline and malignant cases of adrenocortical tumors

Adrenal Carcinoma Treatment

• Surgery is the main treatment
• Medical
• Mitotane
• Adjuvant treatment
• Advanced disease
• Close monitoring
• Hormone replacement
• Radiation therapy
• positive margins
• Palliative treatment
• Cytotoxic therapy
• etoposide
• doxorubicin
• cisplatin
• mitotane