GLYCOGEN STORAGE DISEASES

Type Enzyme Deficiency Major clinical features

(Tissue Affected)
I (von Gierke) Glucose-6 Hepatomegaly, lactic acidosis,
phosphatase Hyperlipidemia, severe fasting,
(liver, kidney) Hypoglycemia

II (Pompe) a-1,4-glucosidase Cardiomegaly, muscles

(all tissues esp. weakness,
muscles) Death in infancy and adult

III (Cori-Forbes) Debrancher (all Hepatomegaly, muscle

tissues) weakness,
Fasting hypoglycemia

IV (Andersen) Brancher (all Portal cirrhosis, death in infancy

tissues)
V (Mc Phosphorylase (muscle) Pain and stiffness after exertion;
Ardle) myoglobinuria
VI (Hers) Phosphorylase (liver) Hepatomegaly, mild fasting
hypoglycemia
VII (Tarui) Phosphofructokinase Pain and stiffness on exertion
(muscles, liver)
VIII Adenylate kinase (liver, Spasticity, decerebration, high
brain) urinary
Catecholamines, death in infancy
IX Phosphorylase kinase Hepatomegaly, occasional fasting
(liver) hypoglycemia
X Cyclic AMP-dependent Hepatomegaly only
Kinase (liver, muscles)
The glycogen storage diseases that can be
detected by intramuscular injection of 100 µ/kg of
glucagon (1 mg maximum) include types I, III, and
VI diseases.

Serial blood specimens are collected for two

hours at 15-minute intervals.

Normal response is a glucose rise of 60-80

mg/dL (3.3-4.4 mmol/L) in 15-30 minutes with no
change in lactate.
In type 1, fasting patients show no increase in
glucose and there is a sharp increase in lactate
within 30-60 minutes.

In type II and type III , glucose response fails but

lactate response is normal.

Definitive diagnosis is done by assay of the

specific enzymes involved.
THYROID NEOPLASMS
Clinically: solitary thyroid nodule (STN)
Benign: Malignant (10:1)
<1% of STNs are malignant
Clinical characteristics that favour malignancy
Solitary nodule
Young
Male
History of radiation therapy
Non-functional nodules (“ cold nodules”)

ADENOMA
Adenoma, follicular hyperplasia and follicular carcinomas: same appeareance
Adenomas are generally not precursors of carcinomas; but share the same genetic
abnormalities
Usually non-functional, but some present with thyrotoxicosis (toxic adenomas)
Morphology
Looks like “normal” follicular epithelial cells; may exhibit Hurthle/ oxyphil change
Atypia and extensive mitosis: Investigate for Follicular Ca or Follicular variant
of papillary Ca
Tumor is enclosed by an intact, well-formed capsule
Absent capsule: Multinodular goiter
Capsular and vascular invasion: Follicular carcinoma
THYROID CARCINOMA
Most common: Papillary (>85%)
Follicular variant of Papillary Ca led to decreases incidence of Follicular Ca
Second most common: Follicular (5-15%)

Most arise from thyroid follicular epithelium (except Medullary (parafollicular C cells));
most are well-differentiated (Anaplastic usually <5%)
Clinically, mass effect
In widely infiltrative lesions, symptoms related to tumor extension
Usually “cold” nodules on scintiscan, except follicular (“warm”)
Medullary thyroid carcinoma (MTC)
Associated with MEN2
Clinically present with paraneoplastic syndromes = Vasoactive intestinal peptide (VIP),
(ACTH) and high levels of calcitonin ( but usually without hypocalcemia)

Prognosis depends on type:

Generally favourable
Papillary
Minimally invasive follicular
Generally unfavourable
Widely invasive follicular
Anaplastic
Medullary
 CARCIN HISTOLOGY
OMA
Papillary  Papillary fronds with fibrovascular cores
 Optically clear nuclei (Ground glass: Orphan Annie nuclei)
M  Calcifications ( Psammoma bodies)
O  Lymphatic invasion
R Follicular  Cytologically similar to normal follicular cells; maybe dominated by
P Hurthle cells (onocytic variant)
H  Minimally invasive: Adenoma + capsular/ vascular invasion
O  Widely invasive: Increased mitosis, less follicular differentiation
L Anaplas  Pleomorphic giant cells (osteoclast-like multinucleated giant cells)
O tic  Spindle-shaped cells (sarcomatous appearance)
G
Y
 Mixed
 Immunostains: (+) cytokeratin, (-) thyroglobulin
medullar  Small, polygonal to spindle-shaped cells
y  Acellular amyloid deposits
 Familial forms: Multicentric, bilateral, (+) parafollicular C cell
hyperplasia
 Sporadic (More common): (-) parafollicular C cell hyperplasia
 MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES

Group of inherited diseases resulting in proliferative lesions of multiple endocrine

tumors

Differences of MEN-associated tumors from sporadic counterparts:

Younger age
Multiple endocrine organs involved at the same time (synchronous) or at different
times (metachronous)
Asymptomatic stage of hyperplasia precedes the tumor
More aggressive and recurrent
 PARAMETER MEN1 MEN2A MEN2B
WERMER SYNDROME SIPPLE SYNDROME
Mutation  Men1  RET (2A and 2B have distinct mutation
Syndrome  Pituitary:  Common: Pheochromocytoma, MTC**
Prolactinomas (MEN2B-associated are more aggressive
(MC) than MEN2A-associated)
 Parathyroid:  MEN2A: Parathyroid hyperplasia
Primary  MEN2B: Neuromas, ganglioneuromas,
hyperparathyroidi Marfanoid habitus
sm (MC; either
adenoma or
hyperplasia)
 Pancreas: PP(MC),
insulinoma or
gastrinoma* (MC)
types that
produce
hypersecretory
states
Genetic  Importance not  Important due to MTC (mortality
well-established prevented by early thyroidectomy)